Search

Your search keyword '"Nussenzweig, Victor"' showing total 486 results
Start Over Author "Nussenzweig, Victor"
486 results on '"Nussenzweig, Victor"'

6. Mapping the Active Site of CD59

Author

Yu, Jinghua, Abagyan, Ruben, Dong, Shanghong, Gilbert, Alexander, Nussenzweig, Victor, and Tomlinson, Stephen

Subjects
Biomedical and Clinical Sciences, Health Sciences, 1.1 Normal biological development and functioning, Underpinning research, Amino Acid Sequence, Animals, Antigens, Surface, Binding Sites, CD59 Antigens, CHO Cells, Carbohydrate Metabolism, Cricetinae, Molecular Sequence Data, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a "hydrophobic strip" suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.

Published
1997

16. Research toward Malaria Vaccines

Author

Miller, Louis H., Howard, Russell J., Carter, Richard, Good, Michael F., Nussenzweig, Victor, and Nussenzweig, Ruth S.

Published
1986

25. A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates

Author

Kubler-Kielb, Joanna, Majadly, Fathy, Biesova, Zuzana, Mocca, Christopher P., Guo, Chunyan, Nussenzweig, Ruth, Nussenzweig, Victor, Mishra, Satish, Wu, Yimin, Miller, Louis H., Keith, Jerry M., Liu, Teh-Yung, Robbins, John B., and Schneerson, Rachel

Subjects
Malaria vaccine -- Research, Immunopharmacology -- Research, Proteins -- Health aspects, Plasmodium falciparum -- Physiological aspects, Science and technology
Abstract

There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum. The circumsporozoite protein (CSP), a major surface antigen of sporozoites, is a protective antigen. A unique feature of P. falciparum CSP is its large central domain composed of over 30 tetrapeptide repeats of Asn-Ala-Asn-Pro (NANP). Several NANP peptide-protein conjugates were tested clinically but elicited a low level of CSP antibodies for a short duration. To provide a CSP-based candidate vaccine, we investigated recombinant CSP and NANP conjugates of various peptide lengths, with different N-terminal amino acids, bound at different ratios to various carrier proteins. Injected into mice, CSP alone and CSP or NANP conjugates induced antibodies with booster responses and were positive by the sporozoite imunofluorescent assay. The use of the mosquito stage P. falciparum ookinete surface protein, Pfs25, cross-linked onto itself as a carrier for NANP, induced in mice high levels of uniquely long-lasting antibodies to both vaccine components with secondary biological activities, that will provide immunity to liver infection by sporozoites and block transmission by mosquitoes. malaria | circumsporozoite protein | Asn-Ala-Asn-Pro | Plasmodium falciparum ookinete surface protein 25 doi/10.1073/pnas.0913374107

Published
2010

27. Aldolase provides an unusual binding site for thrombospondin-related anonymous protein in the invasion machinery of the malaria parasite

Author

Bosch, Jurgen, Buscaglia, Carlos A., Krumm, Brian, Ingason, Bjarni P., Lucas, Robert, Roach, Claudia, Cardozo, Timothy, Nussenzweig, Victor, and Hol, Wim G.J.

Subjects
Fructosediphosphate aldolase -- Research, Malaria -- Research, Protein binding -- Research, Science and technology
Abstract

An actomyosin motor located underneath the plasma membrane drives motility and host-cell invasion of apicomplexan parasites such as Plasmodium falciparum and Plasmodium vivax, the causative agents of malaria. Aldolase connects the motor actin filaments to transmembrane adhesive proteins of the thrombospondin-related anonymous protein (TRAP) family and transduces the motor force across the parasite surface. The TRAP-aldolase interaction is a distinctive and critical trait of host hepatocyte invasion by Plasmodium sporozoites, with a likely similar interaction crucial for erythrocyte invasion by merozoites. Here, we describe 2.4-[Angtrom] and 2.7-[Angtrom] structures of P. falciparum aldolase (PfAIdo) obtained from crystals grown in the presence of the C-terminal hexapeptide of TRAP from Plasmodium berghei. The indole ring of the critical penultimate Trp-residue of TRAP fits snugly into a newly formed hydrophobic pocket, which is exclusively delimited by hydrophilic residues: two arginines, one glutamate, and one glutamine. Comparison with the unliganded PfAIdo structure shows that the two arginines adopt new sidechain rotamers, whereas a 25-residue subdomain, forming a helix-loop-helix unit, shifts upon binding the TRAP-tail. The structural data are in agreement with decreased TRAP binding after mutagenesis of PfAIdo residues in and near the induced TRAP-binding pocket. Remarkably, the TRAP- and actin-binding sites of PfAIdo seem to overlap, suggesting that both the plasticity of the aldolase active-site region and the multimeric nature of the enzyme are crucial for its intriguing nonenzymatic function in the invasion machinery of the malaria parasite. actin | Apicomplexa | cell invasion machinery | gliding motility | induced fit

Published
2007

34. The ubiquitin-proteasome pathway plays an essential role in proteolysis during Trypanosoma cruzi remodeling

Author

Diego, Juana L., Katz, Jeffrey M., Marshall, Patricia, Gutierrez, Bessy, Manning, Jerry E., Nussenzweig, Victor, and Gonzalez, Jorge

Subjects
Trypanosoma cruzi -- Physiological aspects, Proteolysis -- Analysis, Proteases -- Physiological aspects, Ubiquitin -- Physiological aspects, Biological sciences, Chemistry
Abstract

Research shows that during transformation of the Trypanozoma cruzi parasites into amastigotes, proteasome synthesis is enhanced. Data reveal that the 26S proteasome is an 1400 kilo dalton protein exhibiting an ATP-dependent chymotrypsin-like activity and together with ubiquitin it acts on cytoskeletal proteins of the parasite.

Published
2001

39. TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites

Author

Sultan, Ali A., Thathy, Vandana, Frevert, Ute, Robson, Kathryn J.H., Crisanti, Andrea, Nussenzweig, Victor, Nussenzweig, Ruth S., and Menard, Robert

Subjects
Malaria -- Causes of, Parasitic diseases -- Research, Sporozoa -- Physiological aspects, Plasmodium -- Physiological aspects, Biological sciences
Abstract

Researchers have investigated the role of a surface protein called thrombospondin-related anonymous protein (TRAP) in the development of sporozoites and their interactions with host cells. This involved disrupting the TRAP gene in P. berghei. It was established that TRAP-like molecules may be central elements of motility and invasion machineries of Apicomplexa, along with the parasite actin network. It is possible that TRAP may be involved in a capping-like process during cell invasion.

Published
1997

40. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes

Author

Menard, Robert, Sultan, Ali A., Cortes, Claudio, Altszuler, Rita, Dijk, Melissa R. van, Janse, Chris J., Waters, Andrew P., Nussenzweig, Ruth S., and Nussenzweig, Victor

Subjects
Sporozoa -- Physiological aspects, Parasites -- Research, Mosquitoes -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The circumsporozoite (CS) protein appears to be important for malaria parasites in both the vector and the host. One of the major proteins synthesized by salivary gland sporozoites, it is vital in mosquitoes for the development of sporozoites within oocysts. In the vertebrate host, it promotes sporozoite attachment to hepatocytes. These were gleaned from the creation of Plasmodium berghei lines wherein the single-copy CS gene was disrupted. Similar numbers of oocysts of comparable size were produced by the CS(-) and wild-type parasites in the mosquito midgut. However, in the CS(-) oocysts, sporozoite formation was extremely inhibited.

Published
1997

Catalog

Books, media, physical & digital resources
See catalog results