199 results on '"Beddoe T"'
Search Results
2. pertussis toxin in complex with ADPR and Nicotinamide
- Author
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Littler, D.R., primary, Beddoe, T., additional, Pulliainen, A., additional, and Rossjohn, J., additional
- Published
- 2022
- Full Text
- View/download PDF
3. Pertussis toxin in complex with PJ34
- Author
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Littler, D.R., primary, Beddoe, T., additional, Pulliainen, A., additional, and Rossjohn, J., additional
- Published
- 2022
- Full Text
- View/download PDF
4. Pertussis toxin S1 bound to NAD+
- Author
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Littler, D.R., primary, Beddoe, T., additional, Pulliainen, A., additional, and Rossjohn, J., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Pertussis toxin E129D NAD
- Author
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Littler, D.R., primary, Beddoe, T., additional, Pulliainen, A., additional, and Rossjohn, J., additional
- Published
- 2022
- Full Text
- View/download PDF
6. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
- Author
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Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, H, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K, Boehme, K, Brenneisen, P, Brown, J, Dalrymple, B, Harvey, D, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, M, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, O, Kauppila, J, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuiv, P, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, F, Klump, H, Kurgan, L, Smith, S, Terrier, O, Tuttle, N, Ascher, D, Janga, S, Schulte, L, Becker, D, Browngardt, C, Bush, S, Gaullier, G, Ide, K, Meseko, C, Werner, G, Zaucha, J, Al-Farha, A, Greenwald, N, Popoola, S, Rahman, S, Xu, J, Yang, S, Hiroi, N, Alper, O, Baker, C, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K, Lidbury, B, Lin, M, Lynch, I, Ma, W, Maibach, E, Mather, D, Nandakumar, K, Ohgami, R, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, L, Diao, J, Doxey, A, Gobet, A, Hu, P, Kaiser, S, Mitchell, K, Salama, M, Shabalin, I, Song, H, Stevanovic, D, Yadollahpour, A, Zeng, E, Zinke, K, Alimba, C, Beyene, T, Cao, Z, Chan, S, Gatchell, M, Kleppe, A, Piotrowski, M, Torga, G, Woldesemayat, A, Cosacak, M, Haston, S, Ross, S, Williams, R, Wong, A, Abramowitz, M, Effiong, A, Lee, S, Abid, M, Agarabi, C, Alaux, C, Albrecht, D, Atkins, G, Beck, C, Bonvin, A, Bourke, E, Brand, T, Braun, R, Bull, J, Cardoso, P, Carter, D, Delahay, R, Ducommun, B, Duijf, P, Epp, T, Eskelinen, E, Fallah, M, Farber, D, Fernandez-Triana, J, Feyerabend, F, Florio, T, Friebe, M, Furuta, S, Gabrielsen, M, Gruber, J, Grybos, M, Han, Q, Heinrich, M, Helantera, H, Huber, M, Jeltsch, A, Jiang, F, Josse, C, Jurman, G, Kamiya, H, de Keersmaecker, K, Kristiansson, E, de Leeuw, F, Li, J, Liang, S, Lopez-Escamez, J, Lopez-Ruiz, F, Marchbank, K, Marschalek, R, Martin, C, Miele, A, Montagutelli, X, Morcillo, E, Nicoletti, R, Niehof, M, O'Toole, R, Ohtomo, T, Oster, H, Palma, J, Paterson, R, Peifer, M, Portilla, M, Portillo, M, Pritchard, A, Pusch, S, Raghava, G, Roberts, N, Ross, K, Schuele, B, Sergeant, K, Shen, J, Stella, A, Sukocheva, O, Uversky, V, Vanneste, S, Villet, M, Viveiros, M, Vorholt, J, Weinstock, C, Yamato, M, Zabetakis, I, Zhao, X, Ziegler, A, Aizat, W, Atlas, L, Bridges, K, Chakraborty, S, Deschodt, M, Domingues, H, Esfahlani, S, Falk, S, Guisado, J, Kane, N, Kueberuwa, G, Lau, C, Liang, D, Liu, E, Luu, A, Ma, C, Ma, L, Moyer, R, Norris, A, Panthee, S, Parsons, J, Peng, Y, Pinto, I, Reschke, C, Sillanpaa, E, Stewart, C, Uhle, F, Yang, H, Zhou, K, Zhu, S, Ashry, M, Bergsland, N, Berthold, M, Chen, C, Colella, V, Cuypers, M, Eskew, E, Fan, X, Gajda, M, Gonzalezlez-Prendes, R, Goodin, A, Graham, E, Groen, E, Gutierrez-Sacristan, A, Habes, M, Heffler, E, Higginbottom, D, Janzen, T, Jayaraman, J, Jibb, L, Jongen, S, Kinyanjui, T, Koleva-Kolarova, R, Li, Z, Liu, Y, Lund, B, Lussier, A, Mier, P, Moore, M, Nagler, K, Orme, M, Pearson, J, Prajapati, A, Saito, Y, Troder, S, Uchendu, F, Verloh, N, Voutchkova, D, Abu-Zaid, A, Bakkach, J, Baumert, P, Dono, M, Hanson, J, Herbelet, S, Hobbs, E, Kulkarni, A, Liu, S, Loft, N, Reddan, T, Senghore, T, Vindin, H, Xu, H, Bannon, R, Chen, B, Cheung, J, Cooper, J, Esnakula, A, Feghali, K, Ghelardi, E, Gnasso, A, Horbar, J, Lai, H, Ma, R, Pan, Z, Peres, M, Pranata, R, Seow, E, Sydes, M, Testoni, I, Westermair, A, Yang, Y, Afnan, M, Albiol, J, Albuquerque, L, Amir, S, Amiya, E, Amorim, R, An, Q, Andersen, S, Aplin, J, Argyropoulos, C, Asmann, Y, Assaeed, A, Atanasov, A, Atchison, D, Avery, S, Avillach, P, Baade, P, Backman, L, Badie, C, Baldi, A, Ball, E, Bardot, O, Barnett, A, Basner, M, Batra, J, Bazanova, O, Beale, A, Beddoe, T, Bell, M, Berezikov, E, Berners-Price, S, Bernhardt, P, Berry, E, Bessa, T, Billington, C, Birch, J, Blakely, R, Blaskovich, M, Blum, R, Boelaert, M, Bogdanos, D, Bosch, C, Bourgoin, T, Bouvard, D, Boykin, L, Bradley, G, Braun, D, Brownlie, J, Bruhl, A, Burt, A, Butler, L, Byrareddy, S, Byrne, H, Cabantous, S, Calatayud, S, Candal, E, Carlson, K, Casillas, S, Castelvetro, V, Caswell, P, Cavalli, G, Cerovsky, V, Chagoyen, M, Chen, D, Chen, H, Chen, J, Chen, Y, Cheng, C, Cheng, J, Chinapaw, M, Chinopoulos, C, Cho, W, Chong, L, Chowdhury, D, Chwalibog, A, Ciresi, A, Cockcroft, S, Conesa, A, Cook, P, Cooper, D, Coqueret, O, Corea, E, Costa, A, Costa, E, Coupland, C, Crawford, S, Cruz, A, Cui, H, Cui, Q, Culver, D, D'Angiulli, A, Dahms, T, Daigle, F, Dalgleish, R, Danielsen, H, Darras, S, Davidson, S, Day, D, Degirmenci, V, Demaison, L, Devriendt, K, Ding, J, Dogan, Y, Dong, X, Donner, C, Dressick, W, Drevon, C, Duan, H, Ducho, C, Dumaz, N, Dwarakanath, B, Ebell, M, Eisenhardt, S, Elkum, N, Engel, N, Erickson, T, Fairhead, M, Faville, M, Fejzo, M, Festa, F, Feteira, A, Flood-Page, P, Forsayeth, J, Fox, S, Franks, S, Frentiu, F, Frilander, M, Fu, X, Fujita, S, Galea, I, Galluzzi, L, Gani, F, Ganpule, A, Garcia-Alix, A, Gedye, K, Giordano, M, Giunta, C, Gleeson, P, Goarant, C, Gong, H, Gora, D, Gough, M, Goyal, R, Graham, K, Grande-Perez, A, Graves, P, Greidanus, H, Grice, D, Grunau, C, Gumulya, Y, Guo, Y, Gurevich, V, Gusev, O, Hacker, E, Hage, S, Hagen, G, Hahn, S, Haller, D, Hammerschmidt, S, Han, J, Han, R, Handfield, M, Hapuarachchi, H, Harder, T, Hardingham, J, Heck, M, Heers, M, Hew, K, Higuchi, Y, Hilaire, C, Hilton, R, Hodzic, E, Hone, A, Hongoh, Y, Hu, G, Huber, H, Hueso, L, Huirne, J, Hurt, L, Idborg, H, Ikeo, K, Ingley, E, Jakeman, P, Jensen, A, Jia, H, Jia, S, Jiang, J, Jiang, X, Jin, Y, Jo, D, Johnson, A, Johnston, M, Jonscher, K, Jorens, P, Jorgensen, J, Joubert, J, Jung, S, Junior, A, Kahan, T, Kamboj, S, Kang, Y, Karamanos, Y, Karp, N, Kelly, R, Kenna, R, Kennedy, J, Kersten, B, Khalaf, R, Khalid, J, Khatlani, T, Khider, T, Kijanka, G, King, S, Kluz, T, Knox, P, Kobayashi, T, Koch, K, Kohonen-Corish, M, Kong, X, Konkle-Parker, D, Korpela, K, Kostrikis, L, Kraiczy, P, Kratz, H, Krause, G, Krebsbach, P, Kristensen, S, Kumari, P, Kunimatsu, A, Kurdak, H, Kwon, Y, Lachat, C, Lagisz, M, Laky, B, Lammerding, J, Lange, M, Larrosa, M, Laslett, A, Laverman, G, Leclair, E, Lee, K, Lee, M, Li, G, Lieb, K, Lim, Y, Lindsey, M, Line, P, Liu, D, Liu, F, Liu, H, Lloyd, V, Lo, T, Locci, E, Loidl, J, Lorenzen, J, Lorkowski, S, Lovell, N, Lu, H, Lu, W, Lu, Z, Luengo, G, Lundh, L, Lysy, P, Mabb, A, Mack, H, Mackey, D, Mahdavi, S, Maher, P, Maher, T, Maity, S, Malgrange, B, Mamoulakis, C, Mangoni, A, Manke, T, Manstead, A, Mantalaris, A, Marsal, J, Marschall, H, Martin, F, Martinez-Raga, J, Martinez-Salas, E, Mathieu, D, Matsui, Y, Maza, E, Mccutcheon, J, Mckay, G, Mcmillan, B, Mcmillan, N, Meads, C, Medina, L, Merrick, B, Metzger, D, Meunier, F, Michaelis, M, Micheau, O, Mihara, H, Mintz, E, Mizukami, T, Moalic, Y, Mohapatra, D, Monteiro, A, Montes, M, Moran, J, Morozov, S, Mort, M, Murai, N, Murphy, D, Murphy, S, Murray, S, Naganawa, S, Nammi, S, Nasios, G, Natoli, R, Nguyen, F, Nicol, C, van Nieuwerburgh, F, Nilsen, E, Nobile, C, O'Mahony, M, Ohlsson, S, Olatunbosun, O, Olofsson, P, Ortiz, A, Ostrikov, K, Otto, S, Outeiro, T, Ouyang, S, Paganoni, S, Page, A, Palm, C, Paradies, Y, Parsons, M, Parsons, N, Pascal, P, Paul, E, Peckham, M, Pedemonte, N, Pellizzon, M, Petrelli, M, Pichugin, A, Pinto, C, Plevris, J, Pollesello, P, Polz, M, Ponti, G, Porcelli, P, Prince, M, Quinn, G, Quinn, T, Ramula, S, Rappsilber, J, Rehfeldt, F, Reiling, J, Remacle, C, Rezaei, M, Riddick, E, Ritter, U, Roach, N, Roberts, D, Robles, G, Rodrigues, T, Rodriguez, C, Roislien, J, Roobol, M, Rowe, A, Ruepp, A, van Ruitenbeek, J, Rust, P, Saad, S, Sack, G, Santos, M, Saudemont, A, Sava, G, Schrading, S, Schramm, A, Schreiber, M, Schuler, S, Schymkowitz, J, Sczyrba, A, Seib, K, Shi, H, Shimada, T, Shin, J, Shortt, C, Silveyra, P, Skinner, D, Small, I, Smeets, P, So, P, Solano, F, Sonenshine, D, Song, J, Southall, T, Speakman, J, Srinivasan, M, Stabile, L, Stasiak, A, Steadman, K, Stein, N, Stephens, A, Stewart, D, Stine, K, Storlazzi, C, Stoynova, N, Strzalka, W, Suarez, O, Sultana, T, Sumant, A, Summers, M, Sun, G, Tacon, P, Tanaka, K, Tang, H, Tanino, Y, Targett-Adams, P, Tayebi, M, Tayyem, R, Tebbe, C, Telfer, E, Tempel, W, Teodorczyk-Injeyan, J, Thijs, G, Thorne, S, Thrift, A, Tiffon, C, Tinnefeld, P, Tjahjono, D, Tolle, F, Toth, E, Del Tredici, A, Tsapas, A, Tsirigotis, K, Turak, A, Tzotzos, G, Udo, E, Utsumi, T, Vaidyanathan, S, Vaillant, M, Valsesia, A, Vandenbroucke, R, Veiga, F, Vendrell, M, Vesk, P, Vickers, P, Victor, V, Villemur, R, Vohl, M, Voolstra, C, Vuillemin, A, Wakelin, S, Waldron, L, Walsh, L, Wang, A, Wang, F, Wang, Y, Watanabe, Y, Weigert, A, Wen, J, Wham, C, White, E, Wiener, J, Wilharm, G, Wilkinson, S, Willmann, R, Wilson, C, Wirth, B, Wojan, T, Wolff, M, Wong, B, Wu, T, Wuerbel, H, Xiao, X, Xu, D, Xue, B, Yalcin, S, Yan, H, Yang, E, Yang, W, Ye, Y, Ye, Z, Yli-Kauhaluoma, J, Yoneyama, H, Yu, Y, Yuan, G, Yuh, C, Zaccolo, M, Zeng, C, Zevnik, B, Zhang, L, Zhang, Y, Zhao, Y, Zhou, M, Zuberbier, T, Aanei, C, Ahmad, R, Al-Lawama, M, Alanio, A, Allardyce, J, Alonso-Caneiro, D, Atack, J, Baier, D, Bansal, A, Benezeth, Y, Berbesque, C, Berrevoet, F, Biedermann, P, Bijleveld, E, Bittner, F, Blombach, F, van den Bos, W, Boudreau, S, Bramoweth, A, Braubach, O, Cai, Y, Campbell, M, Catry, T, Chen, X, Cheng, S, Chung, H, Chavez-Fumagalli, M, 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- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
- Published
- 2019
7. Fasciola hepatica Control Practices on a Sample of Dairy Farms in Victoria, Australia.
- Author
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Kelley, JM, Rawlin, G, Beddoe, T, Stevenson, M, Spithill, TW, Kelley, JM, Rawlin, G, Beddoe, T, Stevenson, M, and Spithill, TW
- Abstract
In Australia, little is known about the strategies used by farmers to control Fasciola hepatica (F. hepatica) infection in dairy cattle. Triclabendazole-resistant F. hepatica have recently been found on several dairy and beef properties in Australia. It is difficult to draw conclusions about how widespread resistance is in Australian dairy cattle because we have little information about flukicide usage, drug resistance testing, and alternative flukicide usage on-farm. The study objectives were to determine how dairy farmers are currently controlling F. hepatica and to identify knowledge gaps where F. hepatica control strategies need to be communicated to farmers to improve management. The survey was distributed online or by hard copy and 36 dairy farmers completed the survey. There were 34 questions including closed, open-ended, multicheck box, demographic, and text questions. Descriptive statistics were used to quantify each response. The survey results showed high use of clorsulon, limited rotation of flukicides, and limited use of diagnostic tests to inform treatment options and timing. There was poor adherence to best management practice in determining the dose of flukicides administered to cattle, with farmers often relying on estimating body weights or average body weights, suggesting that underdosing of animals is likely to be prevalent. Most respondents in this study did not isolate and quarantine treated and newly returned or purchased animals before joining them with the main herd. The research identified four knowledge gaps where communication needs to be enhanced to improve control of F. hepatica: diagnostic testing to inform flukicide use, rotation of flukicide actives, flukicide administration, and increased testing of replacement animals.
- Published
- 2021
8. The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
- Author
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Sakthivel, D, Preston, S, Gasser, RB, da Costa, TPS, Hernandez, JN, Shahine, A, Shakif-Azam, MD, Lock, P, Rossjohn, J, Perugini, MA, Francisco Gonzalez, J, Meeusen, E, Piedrafita, D, Beddoe, T, Sakthivel, D, Preston, S, Gasser, RB, da Costa, TPS, Hernandez, JN, Shahine, A, Shakif-Azam, MD, Lock, P, Rossjohn, J, Perugini, MA, Francisco Gonzalez, J, Meeusen, E, Piedrafita, D, and Beddoe, T
- Abstract
Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites.
- Published
- 2020
9. Fine structural and functional characterization of a unique IFNβ–Ifnar1 signaling axis: O009
- Author
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De Weerd, N., Nguyen, T., Vivian, J., Mangan, N. E., Gould, J. A., Noppert, S., Zaker-Tabrizi, L., Beddoe, T., Reid, H. H., Rossjohn, J., and Hertzog, P. J.
- Published
- 2012
- Full Text
- View/download PDF
10. The structural basis for autonomous dimerization of the pre-T-cell antigen receptor: P20-78
- Author
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Berry, R., Pang, S., Chen, Z., Kjer-Nielsen, L., Perugini, M., King, G., Wang, C., Chew, S., La Gruta, N., Williams, N., Beddoe, T., Tiganis, T., Cowieson, N., Godfrey, D., Purcell, T., Wilce, M., McCluskey, J., and Rossjohn, J.
- Published
- 2012
11. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
- Author
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Zaritsky, A. Zhang, Y. Zhao, H. Zuckerman, H. Lyu, R. Pullan, W. RELISH Consortium
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press.
- Published
- 2019
12. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
- Author
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H., Vendrell, M., Vesk, P. A., Vickers, P., Victor, V. M., Villemur, R., Vohl, M. -C., Voolstra, C. R., Vuillemin, A., Wakelin, S., Waldron, L., Walsh, L. J., Wang, A. Y., Wang, F., Wang, Y., Watanabe, Y., Weigert, A., Wen, J. -C., Wham, C., White, E. P., Wiener, J., Wilharm, G., Wilkinson, S., Willmann, R., Wilson, C., Wirth, B., Wojan, T. R., Wolff, M., Wong, B. M., Wu, T. -W., Wuerbel, H., Xiao, X., Xu, D., Xu, J. W., Xue, B., Yalcin, S., Yan, H., Yang, E. -C., Yang, S., Yang, W., Ye, Y., Ye, Z. -Q., Yli-Kauhaluoma, J., Yoneyama, H., Yu, Y., Yuan, G. -C., Yuh, C. -H., Zaccolo, M., Zeng, C., Zevnik, B., Zhang, L., Zhang, Y., Zhang, Z. -Y., Zhao, Y., Zhou, M., Zuberbier, T., Aanei, C. M., Ahmad, R., Al-Lawama, M., Alanio, A., Allardyce, J., Alonso-Caneiro, D., Atack, J. M., Baier, D., Bansal, A., Benezeth, Y., Berbesque, C., Berrevoet, F., Biedermann, P. H. W., Bijleveld, E., Bittner, F., Blombach, F., van den Bos, W., Boudreau, S. A., Bramoweth, A. 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D., Pedro, S. A., Perry, S. R., Peter, J., Peterson, B. M., Pezzuolo, A., Pozdnyakov, I., Qian, S., Qin, L., Rafe, A., Raote, I., Raza, A., Rebl, H., Refai, O., Regan, T., Richa, T., Richardson, M. F., Robinson, K. R., Rossoni, L., Rouet, R., Safaei, S., Schneeberger, P. H. H., Schwotzer, D., Sebastian, A., Selinski, J., Seltmann, S., Sha, F., Shalev, N., Shang, J. -L., Singer, J., Singh, M., Smith, T., Solomon-Moore, E., Song, L., Soraggi, S., Stanley, R., Steckhan, N., Strobl, F., Subissi, L., Supriyanto, I., Surve, C. R., Suzuki, T., Syme, C., Sorelius, K., Tang, Y., Tantawy, M., Tennakoon, S., Teseo, S., Toelzer, C., Tomov, N., Tovar, M., Tran, L., Tripathi, S., Tuladhar, A. M., Ukubuiwe, A. C., Ung, C. O. L., Valgepea, K., Vatanparast, H., Vidal, A., Wang, Q., Watari, R., Webster, R., Wei, J., Wibowo, D., Wingenbach, T. S. H., Xavier, R. M., Xiao, S., Xiong, P., Xu, S., Yao, R., Yao, W., Yin, Q., Zaitsu, M., Zeineb, Z., Zhan, X. -Y., Zhang, R., Zhang, W., Zheng, S., Zhou, B., Ahmad, H., Akinwumi, S. A., Albery, G. F., Alhowimel, A., Ali, J., Alshehri, M., Alsuhaibani, M., Anikin, A., Azubuike, S. O., Bach-Mortensen, A., Baltiansky, L., Bartas, M., Belachew, K. Y., Bhardwaj, V., Binder, K., Bland, N. S., Boah, M., Bullen, B., Calabro', Giovanna Elisa, Callahan, T. J., Cao, B., Chalmers, K., Chang, W., Che, Z., Chen, A. T. Y., Chen, Z., Choi, Y., Chowdhury, M. A. K., Christensen, M. R., Cooke, R. S. C., Cottini, M., Covington, N. V., Cunningham, C., Delarocque, J., Devos, L., Dhar, A. R., Ding, K. -F., Dong, K., Dong, Z., Dreyer, N., Ekstrand, C., Fardet, T., Feleke, B. E., Feurer, T., Freitas, A., Gao, T., Gebremedhin, Giganti, F., Grabowski, P., Guerra-Mora, J. R., Guo, C., Guo, X., Gupta, H., He, S., Heijne, M., Heinemann, S., Hogrebe, A., Huang, Z., Iskander-Rizk, S., Iyer, L. M., Jahan, Y., James, A. S., Joel, E., Joffroy, B., Jegousse, C., Kambondo, G., Karnati, P., Kaya, C., Ke, A., Kelly, D., Kickert, R., Kidibule, P. E., Kieselmann, J. P., Kim, H. J., Kitazawa, T., Lamberts, A., Liang, H., Linn, S. N., Litfin, T., Liusuo, W., Lygirou, V., Mahato, A. K., Mai, Z. -M., Major, R. W., Mali, S., Mallis, P., Mao, W., Marvin-Dowle, K., Mason, L. D., Merideth, B., Merino-Plaza, M. J., Merlaen, B., Messina, R., Mishra, A. K., Muhammad, J., Musinguzi, C., Nanou, A., Naqash, A., Nguyen, J. T., Nguyen, T. T. H., Ni, D., Nida, Notcovich, S., Ohst, B., Ollivier, Q. R., Osses, D. F., Peng, X., Plantinga, A., Pulia, M., Rafiq, M., Raman, A., Raucher-Chene, Rawski, R., Ray, A., Razak, L. A., Rudolf, K., Rusch, P., Sadoine, M. L., Schmidt, A., Schurr, R., Searles, S., Sharma, S., Sheehan, B., Shi, C., Shohayeb, B., Sommerlad, A., Strehlow, J., Sun, X., Sundar, R., Taherzadeh, G., Tahir, N. D. M., Tang, J., Testa, J., Tian, Z., Tingting, Q., Verheijen, G. P., Vickstrom, C., Wang, T., Wang, X., Wang, Z., Wei, P., Wilson, A., Wyart, Yassine, A. -A., Yousefzadeh, A., Zare, A., Zeng, Z., Zhang, H., Zhou, J., Zhu, D., Adamo, V., Adeyemo, A. A., Aggelidou, M., Al-Owaifeer, A. M., Al-Riyami, A. Z., Alzghari, S. K., Andersen, V., Angus, K., Asaduzzaman, M., Asady, H., Ato, D., Bai, X., Baines, R. L., Ballantyne, M., Ban, B., Beck, J., Ben-Nafa, W., Black, E., Blancher, A., Blankstein, R., Bodagh, N., Borges, P., Brooks, A., Brox-Ponce, J., Brunetti, A., Canham, C. D., Carninci, P., Carvajal, R., Chang, S. C., Chao, J., Chatterjee, P., Chen, L., Chhatriwalla, A. K., Chikowe, I., Chuang, T. -J., Collevatti, R. G., Cornejo, D. A. V., Cuenda, A., Dao, M., Dauga, D., Deng, Z., Devkota, K., Doan, L. V., Elewa, Y. H. A., Fan, D., Faruk, M., Feifei, S., Ferguson, T. S., Fleres, F., Foster, E. J., Foster, S., Furer, T., Gao, Y., Garcia-Rivera, E. J., Gazdar, A., George, R. B., Ghosh, S., Gianchecchi, E., Gleason, J. M., Hackshaw, A., Hall, A., Hall, R., Harper, P., Hogg, W. E., Huang, G., Hunter, K. E., Ijzerman, A. P., Jesus, C., Jian, G., Lewis, J. S., Kanj, S. S., Kaur, H., Kheir, F., Kichatova, V. S., Kiyani, M., Klein, R., Kovesi, T., Kraschnewski, J. L., Kumar, A. P., Labutin, D., Lazo-Langner, A., Leclercq, G., Li, M., Li, Q., Li, T., Liao, W. -T., Liao, Z. -Y., Lin, J., Lizer, J., Lobreglio, G., Lowies, C., Lu, C., Majeed, H., Martin, A., Martinez-Sobrido, L., Meresh, E., Middelveen, M., Mohebbi, A., Mota, J., Mozaheb, Z., Muyaya, L., Nandhakumar, A., Ng, S. H. X., Obeidat, M., Oh, D. -H., Owais, M., Pace-Asciak, P., Panwar, A., Patterson, C., Penagos-Tabaree, F., Pianosi, P. T., Pinzi, V., Pridans, C., Psaroulaki, A., Pujala, R. K., Pulido-Arjona, L., Qi, P. -F., Rahman, P., Rai, N. K., Rassaf, T., Refardt, J., Ricciardi, Walter, Riess, O., Rovas, A., Sacks, F. M., Saleh, S., Sampson, C., Schmutz, A., Sepanski, R., Sharma, N., Spearman, P., Subramaniapillai, M., Swali, R., Tan, C. M., Tellechea, J. I., Thomas, L. -M., Tong, X., Vavvas, D. G., Veys, R., Vitriol, V., Wang, H. -D., Waugh, J., Webb, S. A., Williams, B. A., Workman, A. D., Xiang, T., Xie, L. -X., Xu, T., Yang, C., Yoon, J. G., Yuan, C. M., Zaritsky, A., Zhao, H., Zuckerman, H., Lyu, R., Pullan, W., Calabro G. E. (ORCID:0000-0003-0259-3797), and Ricciardi W. (ORCID:0000-0002-5655-688X)
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
- Published
- 2019
13. Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus
- Author
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Sakthivel, D, Swan, J, Preston, S, Shakif-Azam, MD, Faouc, P, Jiao, Y, Downs, R, Rajapaksha, H, Gasser, R, Piedrafita, D, Beddoe, T, Sakthivel, D, Swan, J, Preston, S, Shakif-Azam, MD, Faouc, P, Jiao, Y, Downs, R, Rajapaksha, H, Gasser, R, Piedrafita, D, and Beddoe, T
- Abstract
Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins) when compared to the larval stage (two proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS-14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.
- Published
- 2018
14. EcPltAB Oxidized
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Littler, D.R., primary, Johnson, M.D., additional, Summers, R.J., additional, Schembri, M.A., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2016
- Full Text
- View/download PDF
15. EcPltA
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Littler, D.R., primary, Johnson, M.D., additional, Summers, R.J., additional, Schembri, M.A., additional, Rossjohn, J., additional, and Beddoe, T., additional
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- 2016
- Full Text
- View/download PDF
16. Crystal structure of a Mycobacterial protein
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Shahine, A., primary, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2016
- Full Text
- View/download PDF
17. L-fuculose 1-phosphate aldolase from Glaciozyma antarctica PI12
- Author
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Jaafar, N.R., primary, Abu Bakar, F.D., additional, Abdul Murad, A.M., additional, Illias, R., additional, Littler, D., additional, Beddoe, T., additional, Rossjohn, J., additional, and Mahadi, M.N., additional
- Published
- 2015
- Full Text
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18. Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from Legionella pneumophila; substrate specificity and requirement for virulence
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Sansom, F. M., Riedmaier, P., Newton, H. J., Dunstone, M. A., Müller, C. E., Stephan, H., Byres, E., Beddoe, T., Rossjohn, J., Cowan, P. J., D'Apice, A. J. F., Robson, S. C., and Hartland, E. L.
- Abstract
Legionella pneumophila is the predominant cause of Legionnaires disease, a severe and potentially fatal form of pneumonia. Recently, we identified an ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila, termed Lpg1905, which enhances intracellular replication of L. pneumophila in eukaryotic cells. Lpg1905 is the first prokaryotic member of the CD39/NTPDase1 family of enzymes that are characterized by the presence of five apyrase-conserved regions (ACR) and the ability to hydrolyse nucleoside tri- and diphosphates. Here we examined the substrate specificity of Lpg1905 and showed that apart from ATP and ADP, the enzyme catalysed the hydrolysis of GTP and GDP but had limited activity against CTP, CDP, UTP and UDP. Based on amino acid residues conserved in the ACR regions of eukaryotic NTPDases, we generated five site directed mutants, Lpg1905E159A, R122A, N168A, Q193A and W384A. While the mutations, E159A, R122A, Q193A and W384A abrogated activity completely, N168A resulted in decreased activity because of less affinity for nucleotides. When introduced into the lpg1905 mutant strain of L. pneumophila, only N168A (and not the isoforms E159A, R122A, Q193A and W384A) partially restored the ability of L. pneumophila to replicate in THP-1 macrophages. Following intratracheal inoculation of A/J mice, none of the Lpg1905E159A, R122A, Q193A, W384A or N168A isoforms were able to restore virulence to an lpg1905 mutant during lung infection, thereby demonstrating the importance of NTPDase activity to L. pneumophila infection. In addition, the kinetic studies undertaken here demonstrated important differences to mammalian NTPDases, which may be exploited in the design of novel inhibitory compounds to microbial NTPDases for use as anti-infective agents.
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- 2008
19. Recognition of the non-classical MHC class I molecule, HLA-E, by the adaptive immune system
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Hoare, H., Sullivan, Lc, Pietra, G., Clements, C., Beddoe, T., Lee, E., Kjer-Nielsen, L., Reid, H., Mccluskey, J., Moretta, L., Jamie Rossjohn, and Brooks, Ag
- Published
- 2005
20. The role of peptide in the recognition of HLA-E by cytomegalovirus-specific CD8+T cells
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Sullivan, L. C., Lee, E. J., Beddoe, T., Hoare, H. L., Kjer Nielsen, L., Pietra, Gabriella, Moretta, Lorenzo, Rossjohn, J., and Brooks, A. G.
- Published
- 2005
21. A structural and functional investigation of a novel protein from Mycobacterium smegmatis implicated in mycobacterial macrophage survivability
- Author
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Shahine, A.E., primary, Littler, D., additional, Brammananath, R., additional, Chan, P.Y., additional, Crellin, P.K., additional, Coppel, R.L., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2014
- Full Text
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22. Structure of the ClpC N-terminal domain from an alkaliphilic Bacillus lehensis G1 species
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Rashid, S.A., primary, Littler, D.R., additional, Illias, R.M., additional, Murad, A.M.A., additional, Rossjohn, J., additional, Beddoe, T., additional, and Mahadi, N.M., additional
- Published
- 2014
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23. A structural characterization of the isoniazid Mycobacterium tuberculosis drug target, Rv2971, in its unliganded form
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Shahine, A., primary and Beddoe, T., additional
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- 2014
- Full Text
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24. Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition
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Archbold, JK, Macdonald, WA, Gras, S, Ely, LK, Miles, JJ, Bell, MJ, Brennan, RM, Beddoe, T, Wilce, MCJ, Clements, CS, Purcell, AW, McCluskey, J, Burrows, SR, Rossjohn, J, Archbold, JK, Macdonald, WA, Gras, S, Ely, LK, Miles, JJ, Bell, MJ, Brennan, RM, Beddoe, T, Wilce, MCJ, Clements, CS, Purcell, AW, McCluskey, J, Burrows, SR, and Rossjohn, J
- Abstract
Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405(EENLLDFVRF) complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.
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- 2009
25. A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR
- Author
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Wun, KS, Borg, NA, Kjer-Nielsen, L, Beddoe, T, Koh, R, Richardson, SK, Thakur, M, Howell, AR, Scott-Browne, JP, Gapin, L, Godfrey, DI, McCluskey, J, Rossjohn, J, Wun, KS, Borg, NA, Kjer-Nielsen, L, Beddoe, T, Koh, R, Richardson, SK, Thakur, M, Howell, AR, Scott-Browne, JP, Gapin, L, Godfrey, DI, McCluskey, J, and Rossjohn, J
- Abstract
Although it has been established how CD1 binds a variety of lipid antigens (Ag), data are only now emerging that show how alphabeta T cell receptors (TCRs) interact with CD1-Ag. Using the structure of the human semiinvariant NKT TCR-CD1d-alpha-galactosylceramide (alpha-GalCer) complex as a guide, we undertook an alanine scanning mutagenesis approach to define the energetic basis of this interaction between the NKT TCR and CD1d. Moreover, we explored how analogues of alpha-GalCer affected this interaction. The data revealed that an identical energetic footprint underpinned the human and mouse NKT TCR-CD1d-alpha-GalCer cross-reactivity. Some, but not all, of the contact residues within the Jalpha18-encoded invariant CDR3alpha loop and Vbeta11-encoded CDR2beta loop were critical for recognizing CD1d. The residues within the Valpha24-encoded CDR1alpha and CDR3alpha loops that contacted the glycolipid Ag played a smaller energetic role compared with the NKT TCR residues that contacted CD1d. Collectively, our data reveal that the region distant to the protruding Ag and directly above the F' pocket of CD1d was the principal factor in the interaction with the NKT TCR. Accordingly, although the structural footprint at the NKT TCR-CD1d-alpha-GalCer is small, the energetic footprint is smaller still, and reveals the minimal requirements for CD1d restriction.
- Published
- 2008
26. CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
- Author
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Petrie, EJ, Clements, CS, Lin, J, Sullivan, LC, Johnson, D, Huyton, T, Heroux, A, Hoare, HL, Beddoe, T, Reid, HH, Wilce, MCJ, Brooks, AG, Rossjohn, J, Petrie, EJ, Clements, CS, Lin, J, Sullivan, LC, Johnson, D, Huyton, T, Heroux, A, Hoare, HL, Beddoe, T, Reid, HH, Wilce, MCJ, Brooks, AG, and Rossjohn, J
- Abstract
The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a "lock and key" interaction is typical of innate receptor-ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.
- Published
- 2008
27. Apo form of AB5 holotoxin
- Author
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Littler, D.R., primary, Ng, N.M., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2013
- Full Text
- View/download PDF
28. GM1 bound form of the ECX AB5 holotoxin
- Author
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Littler, D.R., primary, Ng, N.M., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2013
- Full Text
- View/download PDF
29. Structural basis of subtilase cytotoxin SubAB assembly
- Author
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Le Nours, J., primary, Paton, A.W., additional, Byres, E., additional, Troy, S., additional, Herdman, B.P., additional, Johnson, M.D., additional, Paton, J.C., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2013
- Full Text
- View/download PDF
30. Structure of human MAIT TCR in complex with human MR1-RL-6-Me-7-OH
- Author
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Patel, O., primary, Kjer-Nielsen, L., additional, Le Nours, J., additional, Eckle, S.B.G., additional, Birkinshaw, R.W., additional, Beddoe, T., additional, Corbett, A.J., additional, Liu, L., additional, Miles, J.J., additional, Meehan, B., additional, Reantragoon, R., additional, Sandoval-Romero, M.L., additional, Sullivan, L.C., additional, Brooks, A.G., additional, Chen, Z., additional, Fairlie, D.P., additional, McCluskey, J., additional, and Rossjohn, J., additional
- Published
- 2013
- Full Text
- View/download PDF
31. Structure of human MAIT TCR in complex with human MR1-6-FP
- Author
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Patel, O., primary, Kjer-Nielsen, L., additional, Le Nours, J., additional, Eckle, S.B.G., additional, Birkinshaw, R.W., additional, Beddoe, T., additional, Corbett, A.J., additional, Liu, L., additional, Miles, J.J., additional, Meehan, B., additional, Reantragoon, R., additional, Sandoval-Romero, M.L., additional, Sullivan, L.C., additional, Brooks, A.G., additional, Chen, Z., additional, Fairlie, D.P., additional, McCluskey, J., additional, and Rossjohn, J., additional
- Published
- 2013
- Full Text
- View/download PDF
32. Crystal structure of the activating Ly49H receptor in complex with m157 (G1F strain)
- Author
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Berry, R., primary, Ng, N., additional, Saunders, P.M., additional, Vivian, J.P., additional, Lin, J., additional, Deuss, F.A., additional, Corbett, A.J., additional, Forbes, C.A., additional, Widjaja, J.M., additional, Sullivan, L.C., additional, McAlister, A.D., additional, Perugini, M.A., additional, Call, M.J., additional, Scalzo, A.A., additional, Degli-Esposti, M.A., additional, Coudert, J.D., additional, Beddoe, T., additional, Brooks, A.G., additional, and Rossjohn, J., additional
- Published
- 2013
- Full Text
- View/download PDF
33. A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
- Author
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Kjer-Nielsen, L, Borg, NA, Pellicci, DG, Beddoe, T, Kostenko, L, Clements, CS, Williamson, NA, Smyth, MJ, Besra, GS, Reid, HH, Bharadwaj, M, Godfrey, DI, Rossjohn, J, McCluskey, J, Kjer-Nielsen, L, Borg, NA, Pellicci, DG, Beddoe, T, Kostenko, L, Clements, CS, Williamson, NA, Smyth, MJ, Besra, GS, Reid, HH, Bharadwaj, M, Godfrey, DI, Rossjohn, J, and McCluskey, J
- Abstract
Little is known regarding the basis for selection of the semi-invariant alphabeta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR alpha- and semi-invariant beta-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant alphabeta TCR and the unique antigen specificity of NKT cells.
- Published
- 2006
34. Structural basis for a major histocompatibility complex class Ib-restricted T cell response
- Author
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Hoare, HL, Sullivan, LC, Pietra, G, Clements, CS, Lee, EJ, Ely, LK, Beddoe, T, Falco, M, Kjer-Nielsen, L, Reid, HH, McCluskey, J, Moretta, L, Rossjohn, J, Brooks, AG, Hoare, HL, Sullivan, LC, Pietra, G, Clements, CS, Lee, EJ, Ely, LK, Beddoe, T, Falco, M, Kjer-Nielsen, L, Reid, HH, McCluskey, J, Moretta, L, Rossjohn, J, and Brooks, AG
- Abstract
In contrast to antigen-specific immunity orchestrated by major histocompatibility complex (MHC) class Ia molecules, the ancestrally related nonclassical MHC class Ib molecules generally mediate innate immune responses. Here we have demonstrated the structural basis by which the MHC class Ib molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte response to human cytomegalovirus. Highly constrained by host genetics, the response showed notable fine specificity for position 8 of the viral peptide, which is the sole discriminator of self versus nonself. Despite the evolutionary divergence of MHC class Ia and class Ib molecules, the structure of the T cell receptor-MHC class Ib complex was very similar to that of conventional T cell receptor-MHC class Ia complexes. These results emphasize the evolutionary 'ambiguity' of HLA-E, which not only interacts with innate immune receptors but also has the functional capacity to mediate virus-specific cytotoxic T lymphocyte responses during adaptive immunity.
- Published
- 2006
35. The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition
- Author
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Borg, NA, Ely, LK, Beddoe, T, Macdonald, WA, Reid, HH, Clements, CS, Purcell, AW, Kjer-Nielsen, L, Miles, JJ, Burrows, SR, McCluskey, J, Rossjohn, J, Borg, NA, Ely, LK, Beddoe, T, Macdonald, WA, Reid, HH, Clements, CS, Purcell, AW, Kjer-Nielsen, L, Miles, JJ, Burrows, SR, McCluskey, J, and Rossjohn, J
- Abstract
The energetic bases of T cell recognition are unclear. Here, we studied the 'energetic landscape' of peptide-major histocompatibility complex (pMHC) recognition by an immunodominant alphabeta T cell receptor (TCR). We quantified and evaluated the effect of natural and systematic substitutions in the complementarity-determining region (CDR) loops on ligand binding in the context of the structural detail of each component of the immunodominant TCR-pMHC complex. The CDR1 and CDR2 loops contributed minimal energy through direct recognition of the antigen and instead had a chief function in stabilizing the ligated CDR3 loops. The underlying energetic basis for recognition lay in the CDR3 loops. Therefore the energetic burden of the CDR loops in the TCR-pMHC interaction is variable among TCRs, reflecting the inherent adaptability of the TCR in ligating different ligands.
- Published
- 2005
36. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide
- Author
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Tynan, FE, Burrows, SR, Buckle, AM, Clements, CS, Borg, NA, Miles, JJ, Beddoe, T, Whisstock, JC, Wilce, MC, Silins, SL, Burrows, JM, Kjer-Nielsen, L, Kostenko, L, Purcell, AW, McCluskey, J, Rossjohn, J, Tynan, FE, Burrows, SR, Buckle, AM, Clements, CS, Borg, NA, Miles, JJ, Beddoe, T, Whisstock, JC, Wilce, MC, Silins, SL, Burrows, JM, Kjer-Nielsen, L, Kostenko, L, Purcell, AW, McCluskey, J, and Rossjohn, J
- Abstract
Unusually long major histocompatibility complex (MHC) class I-restricted epitopes are important in immunity, but their 'bulged' conformation represents a potential obstacle to alphabeta T cell receptor (TCR)-MHC class I docking. To elucidate how such recognition is achieved while still preserving MHC restriction, we have determined here the structure of a TCR in complex with HLA-B(*)3508 presenting a peptide 13 amino acids in length. This complex was atypical of TCR-peptide-MHC class I interactions, being dominated at the interface by peptide-mediated interactions. The TCR assumed two distinct orientations, swiveling on top of the centrally bulged, rigid peptide such that only limited contacts were made with MHC class I. Although the TCR-peptide recognition resembled an antibody-antigen interaction, the TCR-MHC class I contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our findings simultaneously demonstrate the considerable adaptability of the TCR and the 'shape' of MHC restriction.
- Published
- 2005
37. O009 Fine structural and functional characterization of a unique IFNβ–Ifnar1 signaling axis
- Author
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De Weerd, N., primary, Nguyen, T., additional, Vivian, J., additional, Mangan, N.E., additional, Gould, J.A., additional, Noppert, S., additional, Zaker-Tabrizi, L., additional, Beddoe, T., additional, Reid, H.H., additional, Rossjohn, J., additional, and Hertzog, P.J., additional
- Published
- 2012
- Full Text
- View/download PDF
38. A biophysical analysis of the tetratricopeptide repeat-rich mitochondrial import receptor, Tom70, reveals an elongated monomer that is inherently flexible, unstable, and unfolds via a multistate pathway
- Author
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Beddoe, T, Bushell, SR, Perugini, MA, Lithgow, T, Mulhern, TD, Bottomley, SP, Rossjohn, J, Beddoe, T, Bushell, SR, Perugini, MA, Lithgow, T, Mulhern, TD, Bottomley, SP, and Rossjohn, J
- Abstract
Proteins destined for all submitochondrial compartments are translocated across the outer mitochondrial membrane by the TOM (translocase of the outer membrane) complex, which consists of a number of specialized receptor subunits that bind mitochondrial precursor proteins for delivery into the translocation channel. One receptor, Tom70, binds large, hydrophobic mitochondrial precursors. The current model of Tom70-mediated import involves multiple dimers of the receptor recognizing a single molecule of substrate. Here we show via a battery of biophysical and spectroscopic techniques that the cytosolic domain of Tom70 is an elongated monomer. Thermal and urea-induced denaturation revealed that the receptor, which unfolds via a multistate pathway, is a relatively unstable molecule undergoing major conformational change at physiological temperatures. The data suggest that the malleability of the monomeric Tom70 receptor is an important factor in mitochondrial import.
- Published
- 2004
39. Natural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion
- Author
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Zernich, D, Purcell, AW, Macdonald, WA, Kjer-Nielsen, L, Ely, LK, Laham, N, Crockford, T, Mifsud, NA, Bharadwaj, M, Chang, L, Tait, BD, Holdsworth, R, Brooks, AG, Bottomley, SP, Beddoe, T, Peh, CA, Rossjohn, J, McCluskey, J, Zernich, D, Purcell, AW, Macdonald, WA, Kjer-Nielsen, L, Ely, LK, Laham, N, Crockford, T, Mifsud, NA, Bharadwaj, M, Chang, L, Tait, BD, Holdsworth, R, Brooks, AG, Bottomley, SP, Beddoe, T, Peh, CA, Rossjohn, J, and McCluskey, J
- Abstract
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
- Published
- 2004
40. Structural investigations of a novel bacterial AB5toxin
- Author
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Le, Nours J., primary, Tan, L., additional, Troy, S., additional, Byres, E., additional, Smith, D., additional, Paton, A. W., additional, Paton, J. C., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2011
- Full Text
- View/download PDF
41. The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis
- Author
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Clements, CS, Reid, HH, Beddoe, T, Tynan, FE, Perugini, MA, Johns, TG, Bernard, CCA, Rossjohn, J, Clements, CS, Reid, HH, Beddoe, T, Tynan, FE, Perugini, MA, Johns, TG, Bernard, CCA, and Rossjohn, J
- Abstract
Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopathological role of MOG, we determined the 1.8-A crystal structure of the MOG extracellular domain (MOGED). MOGED adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel head-to-tail dimer. A dimeric form of native MOG was observed, and MOGED was also shown to dimerize in solution, consistent with the view of MOG acting as a homophilic adhesion receptor. The MOG35-55 peptide, a major encephalitogenic determinant recognized by both T cells and demyelinating autoantibodies, is partly occluded within the dimer interface. The structure of this key autoantigen suggests a relationship between the dimeric form of MOG within the myelin sheath and a breakdown of immunological tolerance to MOG that is observed in multiple sclerosis.
- Published
- 2003
42. Crystal Structure of MSMEG_6394
- Author
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Vivian, J.P., primary, Scoble, J., additional, Beddoe, T., additional, and Rossjohn, J., additional
- Published
- 2010
- Full Text
- View/download PDF
43. Crystal structure of a mycobacterium aldo-keto reductase in its apo and liganded form
- Author
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Scoble, J., primary, McAlister, A.D., additional, Fulton, Z., additional, Troy, S., additional, Byres, E., additional, Vivian, J.P., additional, Brammananth, R., additional, Wilce, M.C.J., additional, Le Nours, J., additional, Zaker-Tabrizi, L., additional, Coppel, R.L., additional, Crellin, P.K., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2010
- Full Text
- View/download PDF
44. Crystal structure of Lp1NTPDase from Legionella pneumophila in complex with the inhibitor ARL 67156
- Author
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Vivian, J.P., primary, Beddoe, T., additional, and Rossjohn, J., additional
- Published
- 2010
- Full Text
- View/download PDF
45. Crystal structure of Lp1NTPDase from Legionella pneumophila in complex with AMPPNP
- Author
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Ge, H., primary, Vivian, J.P., additional, Beddoe, T., additional, and Rossjohn, J., additional
- Published
- 2010
- Full Text
- View/download PDF
46. Crystal Structure of Lp1NTPDase from Legionella pneumophila
- Author
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Vivian, J.P., primary, Beddoe, T., additional, and Rossjohn, J., additional
- Published
- 2010
- Full Text
- View/download PDF
47. The oxidoreductase NmDsbA1 from N. meningitidis
- Author
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Vivian, J.P., primary, Scoullar, J., additional, Bushell, S., additional, Beddoe, T., additional, Wilce, M.C.J., additional, Byres, E., additional, Boyle, T.P., additional, Rimmer, K., additional, Doak, B., additional, Simpson, J.S., additional, Graham, B., additional, Heras, B., additional, Kahler, C.M., additional, Rossjohn, J., additional, and Scanlon, M.J., additional
- Published
- 2009
- Full Text
- View/download PDF
48. Crystal structure of LipL32, the most abundant surface protein of pathogenic leptospira spp
- Author
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Vivian, J.P., primary, Beddoe, T., additional, and Rossjohn, J., additional
- Published
- 2009
- Full Text
- View/download PDF
49. Crystal structure of the B-subunit of the AB5 toxin from E. coli
- Author
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Byres, E., primary, Paton, A.W., additional, Paton, J.C., additional, Lofling, J.C., additional, Smith, D.F., additional, Wilce, M.C.J., additional, Talbot, U.M., additional, Chong, D.C., additional, Yu, H., additional, Huang, S., additional, Chen, X., additional, Varki, N.M., additional, Varki, A., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2008
- Full Text
- View/download PDF
50. Crystal structure of the B-subunit of the AB5 toxin from E. Coli with Neu5Gc
- Author
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Byres, E., primary, Paton, A.W., additional, Paton, J.C., additional, Lofling, J.C., additional, Smith, D.F., additional, Wilce, M.C.J., additional, Talbot, U.M., additional, Chong, D.C., additional, Yu, H., additional, Huang, S., additional, Chen, X., additional, Varki, N.M., additional, Varki, A., additional, Rossjohn, J., additional, and Beddoe, T., additional
- Published
- 2008
- Full Text
- View/download PDF
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