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15 results on '"Pacios, Luis F [0000-0002-0585-4289]"'

1. Intrinsic disorder in the dynamic evolution of structure, stability, and flexibility of potyviral VLP assemblies: A computational study

Author

Universidad Politécnica de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Pacios, Luis F. [0000-0002-0585-4289], Ponz Ascaso, Fernando [0000-0003-0344-4363], Pacios, Luis F., Sánchez, Flora, Ponz Ascaso, Fernando, Universidad Politécnica de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Pacios, Luis F. [0000-0002-0585-4289], Ponz Ascaso, Fernando [0000-0003-0344-4363], Pacios, Luis F., Sánchez, Flora, and Ponz Ascaso, Fernando

Abstract

An all-atom Molecular Dynamics (MD) study was applied to three viral nanoparticles (VLPs) of Turnip mosaic virus (TuMV), a potyvirus: the particles genetically functionalized with two peptides, VIP (human vasoactive intestinal peptide) and VEGFR (peptide derived from the human receptor 3 of the vascular endothelial growth factor), and the non-functionalized VLP. Previous experimental results showed that VIP-VLP was the only construct of the three that was not viable. VLPs subjected to our MD study were modeled by four complete turns of the particle involving 35 subunits of the coat protein (CP). The MD simulations showed differences in structures and interaction energies associated to the crucial contribution of the disordered N-terminal arms of CP to the global stability of the particle. These differences suggested an overall stability greater in VEGFR-VLP and smaller in VIP-VLP as compared to the unfunctionalized VLP. Our novel MD study of potyviral VLPs revealed essential clues about structure and interactions of these assembled protein particles and suggests that the computational prediction of the viability of VLPs can be a valuable contribution in the field of viral nanobiotechnology.

Published
2024

2. Synthetically derived BiAux modulates auxin co-receptor activity to stimulate lateral root formation

Author

Ministerio de Ciencia y Tecnología (España), Agencia Estatal de Investigación (España), European Commission, González-García, Mary Paz [0000-0002-3739-3368], Saez, Angela [0000-0002-9189-4737], Lanza, Mónica [0009-0002-5868-9296], Hoyos, Pilar [0000-0001-6053-2437], Bustillo-Avendaño, Estefano [0000-0002-1442-8791], Pacios, Luis F. [0000-0002-0585-4289], Gradillas, Ana [0000-0001-7290-5210], Moreno-Risueño, Miguel Ángel [0000-0002-9794-1450], Hernaiz, María José [0000-0003-3897-1104], Pozo, Juan Carlos del [0000-0002-4113-457X], González-García, Mary Paz, Saez, Angela, Lanza, Mónica, Hoyos, Pilar, Bustillo-Avendaño, Estefano, Pacios, Luis F., Gradillas, Ana, Moreno-Risueño, Miguel Ángel, Hernaiz, María José, Pozo, Juan Carlos del, Ministerio de Ciencia y Tecnología (España), Agencia Estatal de Investigación (España), European Commission, González-García, Mary Paz [0000-0002-3739-3368], Saez, Angela [0000-0002-9189-4737], Lanza, Mónica [0009-0002-5868-9296], Hoyos, Pilar [0000-0001-6053-2437], Bustillo-Avendaño, Estefano [0000-0002-1442-8791], Pacios, Luis F. [0000-0002-0585-4289], Gradillas, Ana [0000-0001-7290-5210], Moreno-Risueño, Miguel Ángel [0000-0002-9794-1450], Hernaiz, María José [0000-0003-3897-1104], Pozo, Juan Carlos del [0000-0002-4113-457X], González-García, Mary Paz, Saez, Angela, Lanza, Mónica, Hoyos, Pilar, Bustillo-Avendaño, Estefano, Pacios, Luis F., Gradillas, Ana, Moreno-Risueño, Miguel Ángel, Hernaiz, María José, and Pozo, Juan Carlos del

Abstract

The root system plays an essential role in plant growth and adaptation to the surrounding environment. The root clock periodically specifies lateral root prebranch sites (PBS), where a group of pericycle founder cells (FC) is primed to become lateral root founder cells and eventually give rise to lateral root primordia or lateral roots (LRs). This clock-driven organ formation process is tightly controlled by modulation of auxin content and signaling. Auxin perception entails the physical interaction of TRANSPORT INHIBITOR RESPONSE 1 (TIR1) or AUXIN SIGNALING F-BOX (AFBs) proteins with AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) repressors to form a co-receptor system. Despite the apparent simplicity, the understanding of how specific auxin co-receptors are assembled remains unclear. We identified the compound bis-methyl auxin conjugated with N-glucoside, or BiAux, in Arabidopsis (Arabidopsis thaliana) that specifically induces the formation of PBS and the emergence of LR, with a slight effect on root elongation. Docking analyses indicated that BiAux binds to F-box proteins, and we showed that BiAux function depends on TIR1 and AFB2 F-box proteins and AUXIN RESPONSE FACTOR 7 activity, which is involved in FC specification and LR formation. Finally, using a yeast (Saccharomyces cerevisiae) heterologous expression system, we showed that BiAux favors the assemblage of specific co-receptors subunits involved in LR formation and enhances AUXIN/INDOLE-3-ACETIC ACID 28 protein degradation. These results indicate that BiAux acts as an allosteric modulator of specific auxin co-receptors. Therefore, BiAux exerts a fine-tune regulation of auxin signaling aimed to the specific formation of LR among the many development processes regulated by auxin.

Published
2024

3. Structural intrinsic disorder in a functionalized potyviral coat protein as a main viability determinant of its assembled nanoparticles

Author

Comunidad de Madrid, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Mínguez-Toral, Marina [0000-0001-7818-7360], Pacios, Luis F [0000-0002-0585-4289], Sánchez, Flora [0000-0002-9440-3323], Ponz, Fernando [0000-0003-0344-4363], Mínguez-Toral, Marina, Pacios, Luis F., Sánchez, Flora, Ponz, Fernando, Comunidad de Madrid, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), European Commission, Mínguez-Toral, Marina [0000-0001-7818-7360], Pacios, Luis F [0000-0002-0585-4289], Sánchez, Flora [0000-0002-9440-3323], Ponz, Fernando [0000-0003-0344-4363], Mínguez-Toral, Marina, Pacios, Luis F., Sánchez, Flora, and Ponz, Fernando

Abstract

The viability of viral-derived nanoparticles (virions and VLPs) aimed to nanobiotechnological functionalizations of the coat protein (CP) of turnip mosaic virus has been studied by means of advanced computational methodologies that include molecular dynamics. The study has allowed to model the structure of the complete CP and its functionalization with three different peptides and obtain essential structural features such as order/disorder, interactions, and electrostatic potentials of their constituent domains. The results provide for the first time a dynamic view of a complete potyvirus CP, since experimental available structures so far obtained lack N- and C-terminal segments. The relevance of disorder in the most distal N-terminal subdomain, and the interaction of the less distal N-terminal subdomain with the highly ordered CP core, stand out as crucial characteristic for a viable CP. Preserving them proved of outmost importance to obtain viable potyviral CPs presenting peptides at their N-terminus.

Published
2023

4. Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity

Author

Biomedical International R+D GmbH, Bencard Allergie GmbH, Danube Allergy Research Cluster, Karl Landsteiner University of Health Sciences, Wiederstein, Markus [0000-0002-4750-4746], Fakhimahmadi, Aila [0000-0002-6804-6238], Pacios, Luis F. [0000-0002-0585-4289], Blokhuis, Bart R. [0000-0002-9366-6404], Redegeld, Frank A. [0000-0001-8830-7960], Hofstetter, Gerlinde [0000-0003-2077-4479], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin [0000-0002-2288-2468], Roth-Walter, Franziska [0000-0001-5005-9228], Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Pacios, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, Roth-Walter, Franziska, Biomedical International R+D GmbH, Bencard Allergie GmbH, Danube Allergy Research Cluster, Karl Landsteiner University of Health Sciences, Wiederstein, Markus [0000-0002-4750-4746], Fakhimahmadi, Aila [0000-0002-6804-6238], Pacios, Luis F. [0000-0002-0585-4289], Blokhuis, Bart R. [0000-0002-9366-6404], Redegeld, Frank A. [0000-0001-8830-7960], Hofstetter, Gerlinde [0000-0003-2077-4479], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin [0000-0002-2288-2468], Roth-Walter, Franziska [0000-0001-5005-9228], Regner, Andreas, Szepannek, Nathalie, Wiederstein, Markus, Fakhimahmadi, Aila, Pacios, Luis F., Blokhuis, Bart R., Redegeld, Frank A., Hofstetter, Gerlinde, Dvorak, Zdenek, Jensen-Jarolim, Erika, Hufnagl, Karin, and Roth-Walter, Franziska

Abstract

Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory properties on human immune cells. Binding of Bet v 1 to iron quercetin complexes FeQ2 was determined in docking calculations and by spectroscopy. Serum IgE-binding to Bet v 1 with (holoBet v1) and without ligands (apoBet v 1) were assessed by ELISA, blocking experiments and Western Blot. Crosslinking-capacity of apo/holoBet v 1 were assessed on human mast cells and Arylhydrocarbon receptor (AhR) activation with the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for labile iron and phenotypic changes by flow cytometry. Bet v 1 bound to FeQ2 strongly with calculated Kd values of 1 nm surpassing affinities to quercetin alone nearly by a factor of 1000. Binding to FeQ2 masked IgE epitopes and decreased IgE binding up to 80% and impaired degranulation of sensitized human mast cells. Bet v 1 facilitated the shuttling of quercetin, which activated the anti-inflammatory AhR pathway and increased the labile iron pool of human monocytic cells. The increase of labile iron was associated with an anti-inflammatory phenotype in CD14+monocytes and downregulation of HLADR. To summarize, we reveal for the first time that FeQ2 binding reduces the allergenicity of Bet v 1 due to ligand masking, but also actively contributes anti-inflammatory stimuli to human monocytes, thereby fostering tolerance. Nourishing immune cells with complex iron may thus represent a promising antigen-independent immunotherapeutic approach to improve efficacy in allergen immunotherapy.

Published
2022

5. Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect

Author

Austrian Science Fund, Biomedical International R+D GmbH, Bencard Allergie GmbH, Pali-Schöll, Isabella [0000-0003-2089-6011], Bianchini, Rodolfo [0000-0003-0351-6937], Afify, Sheriene Moussa [0000-0003-2082-9038], Hofstetter, Gerlinde [0000-0003-2077-4479], Mayerhofer, Hanna [0000-0001-7973-2092], Hufnagl, Karin [0000-0002-2288-2468], Korath, Anna D J [0000-0002-6408-4157], Pranger, Christina [0000-0002-4232-5730], Widhalm, Raimund [0000-0002-8257-9903], Hann, Stephan [0000-0001-5045-7293], Wittek, Thomas [0000-0001-6113-8458], Kasper-Giebl, Anne [0000-0003-2736-2880], Pacios, Luis F [0000-0002-0585-4289], Roth-Walter, Franziska [0000-0001-5005-9228], Vercelli, Donata [0000-0001-5276-8976], von Mutius, Erika [0000-0002-8893-4515], Jensen-Jarolim, Erika [0000-0003-4019-5765], Pali-Schöll, Isabella, Bianchini, Rodolfo, Afify, Sheriene Moussa, Hofstetter, Gerlinde, Winkler, Simona, Ahlers, Stella, Altemeier, Theresa, Mayerhofer, Hanna, Hufnagl, Karin, Korath, Anna D J, Pranger, Christina, Widhalm, Raimund, Hann, Stephan, Wittek, Thomas, Kasper-Giebl, Anne, Pacios, Luis F., Roth-Walter, Franziska, Vercelli, Donata, von Mutius, Erika, Jensen-Jarolim, Erika, Austrian Science Fund, Biomedical International R+D GmbH, Bencard Allergie GmbH, Pali-Schöll, Isabella [0000-0003-2089-6011], Bianchini, Rodolfo [0000-0003-0351-6937], Afify, Sheriene Moussa [0000-0003-2082-9038], Hofstetter, Gerlinde [0000-0003-2077-4479], Mayerhofer, Hanna [0000-0001-7973-2092], Hufnagl, Karin [0000-0002-2288-2468], Korath, Anna D J [0000-0002-6408-4157], Pranger, Christina [0000-0002-4232-5730], Widhalm, Raimund [0000-0002-8257-9903], Hann, Stephan [0000-0001-5045-7293], Wittek, Thomas [0000-0001-6113-8458], Kasper-Giebl, Anne [0000-0003-2736-2880], Pacios, Luis F [0000-0002-0585-4289], Roth-Walter, Franziska [0000-0001-5005-9228], Vercelli, Donata [0000-0001-5276-8976], von Mutius, Erika [0000-0002-8893-4515], Jensen-Jarolim, Erika [0000-0003-4019-5765], Pali-Schöll, Isabella, Bianchini, Rodolfo, Afify, Sheriene Moussa, Hofstetter, Gerlinde, Winkler, Simona, Ahlers, Stella, Altemeier, Theresa, Mayerhofer, Hanna, Hufnagl, Karin, Korath, Anna D J, Pranger, Christina, Widhalm, Raimund, Hann, Stephan, Wittek, Thomas, Kasper-Giebl, Anne, Pacios, Luis F., Roth-Walter, Franziska, Vercelli, Donata, von Mutius, Erika, and Jensen-Jarolim, Erika

Abstract

Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle-specific protein as active component in this farm effect.

Published
2022

6. Machine Learning of Analytical Electron Density in Large Molecules Through Message-Passing

Author

Ministerio de Ciencia e Innovación (España), Universidad Politécnica de Madrid, Banco Santander, Agencia Estatal de Investigación (España), Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Pacios, Luis F. [0000-0002-0585-4289], Cuevas-Zuviría, Bruno, Pacios, Luis F., Ministerio de Ciencia e Innovación (España), Universidad Politécnica de Madrid, Banco Santander, Agencia Estatal de Investigación (España), Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Pacios, Luis F. [0000-0002-0585-4289], Cuevas-Zuviría, Bruno, and Pacios, Luis F.

Abstract

Machine learning milestones in computational chemistry are overshadowed by their unaccountability and the overwhelming zoo of tools for each specific task. A promising path to tackle these problems is using machine learning to reproduce physical magnitudes as a basis to derive many other properties. By using a model of the electron density consisting of an analytical expansion on a linear set of isotropic and anisotropic functions, we implemented in this work a message-passing neural network able to reproduce electron density in molecules with just a 2.5% absolute error in complex cases. We also adapted our methodology to describe electron density in large biomolecules (proteins) and to obtain atomic charges, interaction energies, and DFT energies. We show that electron density learning is a new promising avenue with a variety of forthcoming applications.

Published
2021

7. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A. [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa, Regner, Andreas, Pacios, Luis F., Blokhuis, Bart R., Jensen, Sebastian A, Redegeld, Frank A., Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, and Roth-Walter, Franziska

Abstract

Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

Published
2021

8. Retinoic acid-loading of the major birch pollen allergen Bet v 1 may improve specific allergen immunotherapy: In silico, in vitro and in vivo data in BALB/c mice

Author

Austrian Science Fund, Hufnagl, Karin [0000-0002-2288-2468], Afify, Sheriene M. [0000-0003-2082-9038], Wallner, Michael [0000-0001-6568-7892], Hauser, Michael [0000-0001-6558-755X], Wiederstein, Markus [0000-0002-4750-4746], Gadermaier, Gabriele [0000-0002-4886-417X], Wildner, Sabrina [0000-0003-2348-7598], Redegeld, Frank A. [0000-0001-8830-7960], Blokhuis, Bart R. [0000-0002-9366-6404], Hofstetter, Gerlinde [0000-0003-2077-4479], Pali-Schöll, Isabella [0000-0003-2089-6011], Roth-Walter, Franziska [0000-0001-5005-9228], Pacios, Luis F. [0000-0002-0585-4289], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin, Afify, Sheriene M., Braun, Nina, Wagner, Stefanie, Wallner, Michael, Hauser, Michael, Wiederstein, Markus, Gadermaier, Gabriele, Wildner, Sabrina, Redegeld, Frank A., Blokhuis, Bart R., Hofstetter, Gerlinde, Pali-Schöll, Isabella, Roth-Walter, Franziska, Pacios, Luis F., Jensen-Jarolim, Erika, Austrian Science Fund, Hufnagl, Karin [0000-0002-2288-2468], Afify, Sheriene M. [0000-0003-2082-9038], Wallner, Michael [0000-0001-6568-7892], Hauser, Michael [0000-0001-6558-755X], Wiederstein, Markus [0000-0002-4750-4746], Gadermaier, Gabriele [0000-0002-4886-417X], Wildner, Sabrina [0000-0003-2348-7598], Redegeld, Frank A. [0000-0001-8830-7960], Blokhuis, Bart R. [0000-0002-9366-6404], Hofstetter, Gerlinde [0000-0003-2077-4479], Pali-Schöll, Isabella [0000-0003-2089-6011], Roth-Walter, Franziska [0000-0001-5005-9228], Pacios, Luis F. [0000-0002-0585-4289], Jensen-Jarolim, Erika [0000-0003-4019-5765], Hufnagl, Karin, Afify, Sheriene M., Braun, Nina, Wagner, Stefanie, Wallner, Michael, Hauser, Michael, Wiederstein, Markus, Gadermaier, Gabriele, Wildner, Sabrina, Redegeld, Frank A., Blokhuis, Bart R., Hofstetter, Gerlinde, Pali-Schöll, Isabella, Roth-Walter, Franziska, Pacios, Luis F., and Jensen-Jarolim, Erika

Published
2020

9. Dynamic plasticity of the lipid antigen-binding site of CD1d is crucially favoured by acidic pH and helper proteins

Author

Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Universidad Politécnica de Madrid, Banco Santander, European Commission, Agencia Estatal de Investigación (España), Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Mínguez-Toral, Marina [0000-0001-7818-7360], Díaz-Perales, Araceli [0000-0002-1093-3627], Garrido-Arandía, María [0000-0001-6114-5754], Pacios, Luis F. [0000-0002-0585-4289], Cuevas-Zuviría, Bruno, Mínguez-Toral, Marina, Díaz-Perales, Araceli, Garrido-Arandía, María, Pacios, Luis F., Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Universidad Politécnica de Madrid, Banco Santander, European Commission, Agencia Estatal de Investigación (España), Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Mínguez-Toral, Marina [0000-0001-7818-7360], Díaz-Perales, Araceli [0000-0002-1093-3627], Garrido-Arandía, María [0000-0001-6114-5754], Pacios, Luis F. [0000-0002-0585-4289], Cuevas-Zuviría, Bruno, Mínguez-Toral, Marina, Díaz-Perales, Araceli, Garrido-Arandía, María, and Pacios, Luis F.

Abstract

CD1 molecules present lipid antigens for recognition by T-cell receptors (TCRs). Although a reasonably detailed picture of the CD1-lipid-TCR interaction exists, the initial steps regarding lipid loading onto and exchange between CD1 proteins remain elusive. The hydrophobic nature of lipids and the fact that CD1 molecules are unable to extract lipids from membranes raise the need for the assistance of helper proteins in lipid trafficking. However, the experimental study of this traffic in the endosomal compartments at which it occurs is so challenging that computational studies can help provide mechanistic insight into the associated processes. Here we present a multifaceted computational approach to obtain dynamic structural data on the human CD1d isotype. Conformational dynamics analysis shows an intrinsic flexibility associated with the protein architecture. Electrostatic properties together with molecular dynamics results for CD1d complexes with several lipids and helper proteins unravel the high dynamic plasticity of the antigen-binding site that is crucially favoured by acidic pH and the presence of helper proteins.

Published
2020

10. A computational structural study on the DNA-protecting role of the tardigrade-unique Dsup protein

Author

Universidad Politécnica de Madrid, Banco Santander, European Commission, Centro de Supercomputación y Visualización de Madrid, Agencia Estatal de Investigación (España), Mínguez-Toral, Marina [0000-0001-7818-7360], Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Garrido-Arandía, María [0000-0001-6114-5754], Pacios, Luis F. [0000-0002-0585-4289], Mínguez-Toral, Marina, Cuevas-Zuviría, Bruno, Garrido-Arandía, María, Pacios, Luis F., Universidad Politécnica de Madrid, Banco Santander, European Commission, Centro de Supercomputación y Visualización de Madrid, Agencia Estatal de Investigación (España), Mínguez-Toral, Marina [0000-0001-7818-7360], Cuevas-Zuviría, Bruno [0000-0003-1479-9442], Garrido-Arandía, María [0000-0001-6114-5754], Pacios, Luis F. [0000-0002-0585-4289], Mínguez-Toral, Marina, Cuevas-Zuviría, Bruno, Garrido-Arandía, María, and Pacios, Luis F.

Abstract

The remarkable ability of tardigrades to withstand a wide range of physical and chemical extremes has attracted a considerable interest in these small invertebrates, with a particular focus on the protective roles of proteins expressed during such conditions. The discovery that a tardigrade-unique protein named Dsup (damage suppressor) protects DNA from damage produced by radiation and radicals, has raised expectations concerning its potential applications in biotechnology and medicine. We present in this paper what might be dubbed a "computational experiment" on the Dsup-DNA system. By means of molecular modelling, calculations of electrostatic potentials and electric fields, and all-atom molecular dynamics simulations, we obtained a dynamic picture of the Dsup-DNA interaction. Our results suggest that the protein is intrinsically disordered, which enables Dsup to adjust its structure to fit DNA shape. Strong electrostatic attractions and high protein flexibility drive the formation of a molecular aggregate in which Dsup shields DNA. While the precise mechanism of DNA protection conferred by Dsup remains to be elucidated, our study provides some molecular clues of their association that could be of interest for further investigation in this line.

Published
2020

11. Characterisation of a flavonoid ligand of the fungal protein Alt a 1

Author

Garrido-Arandía, María [0000-0001-6114-5754], Barber, Domingo F. [0000-0001-8824-5405], Díaz-Perales, Araceli [0000-0002-1093-3627], Pacios, Luis F. [0000-0002-0585-4289], Garrido-Arandía, María, Silva-Navas, J., Ramírez, Carmen, Cubells-Baeza, N., Gómez-Casado, Cristina, Barber, Domingo F., del Pozo, J. C., Gonzalez-Melendi, P., Pacios, Luis F., Díaz-Perales, Araceli, Garrido-Arandía, María [0000-0001-6114-5754], Barber, Domingo F. [0000-0001-8824-5405], Díaz-Perales, Araceli [0000-0002-1093-3627], Pacios, Luis F. [0000-0002-0585-4289], Garrido-Arandía, María, Silva-Navas, J., Ramírez, Carmen, Cubells-Baeza, N., Gómez-Casado, Cristina, Barber, Domingo F., del Pozo, J. C., Gonzalez-Melendi, P., Pacios, Luis F., and Díaz-Perales, Araceli

Abstract

Spores of pathogenic fungi are virtually ubiquitous and cause human disease and severe losses in crops. The endophytic fungi Alternaria species produce host-selective phytotoxins. Alt a 1 is a strongly allergenic protein found in A. alternata that causes severe asthma. Despite the well-established pathogenicity of Alt a 1, the molecular mechanisms underlying its action and physiological function remain largely unknown. To gain insight into the role played by this protein in the pathogenicity of the fungus, we studied production of Alt a 1 and its activity in spores. We found that Alt a 1 accumulates inside spores and that its release with a ligand is pH-dependent, with optimum production in the 5.0-6.5 interval. The Alt a 1 ligand was identified as a methylated flavonoid that inhibits plant root growth and detoxifies reactive oxygen species. We also found that Alt a 1 changes its oligomerization state depending on the pH of the surrounding medium and that these changes facilitate the release of the ligand. Based on these results, we propose that release of Alt a 1 should be a pathogenic target in approaches used to block plant defenses and consequently to favor fungal entry into the plant. © 2016 The Author(s).

Published
2016

12. The Arabidopsis cell cycle F-Box protein SKP2A binds to auxin

Author

López-Torrejón, Gema [0000-0003-2588-4378], Pacios, Luis F. [0000-0002-0585-4289], Manzano, Concepción [0000-0003-1592-5068], Jurado, Silvia, Abraham, Z., Manzano, Concepción, López-Torrejón, Gema, Pacios, Luis F., del Pozo, J. C., López-Torrejón, Gema [0000-0003-2588-4378], Pacios, Luis F. [0000-0002-0585-4289], Manzano, Concepción [0000-0003-1592-5068], Jurado, Silvia, Abraham, Z., Manzano, Concepción, López-Torrejón, Gema, Pacios, Luis F., and del Pozo, J. C.

Abstract

Arabidopsis thaliana S-Phase Kinase-Associated Protein 2A (SKP2A) is an F-box protein that regulates the proteolysis of cell cycle transcription factors. The plant hormone auxin regulates multiple aspects of plant growth and development, including cell division. We found that auxin induces the ubiquitin-dependent degradation of SKP2A both in vivo and in vitro, suggesting that this hormone acts as a signal to trigger SKP2A proteolysis. In this article, we show that auxin binds directly and specifically to SKP2A. By TIR1-based superposition and docking analyzes, we identified an auxin binding site in SKP2A. Mutations in this binding site reduce the ability of SKP2A to bind to auxin and generate nondegradable SKP2A forms. In addition, these non-auxin binding proteins are unable to promote E2FC/DPB degradation in vivo or to induce cell division in the root meristem. Auxin binds to TIR1 to promote its interaction with the auxin/indole-3-acetic acid target proteins. Here, we show that auxin also enhanced the interaction between SKP2A and DPB. Finally, a mutation in SKP2A leads to auxinresistant root growth, an effect that is additive with the tir1-1 phenotype. Thus, our data indicate that SKP2A is an auxin binding protein that connects auxin signaling with cell division.

Published
2010

13. Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Author

Karin Hufnagl, Erika Jensen-Jarolim, Rodolfo Bianchini, Andreas Regner, Franziska Roth-Walter, Zdenek Dvorak, Luis F. Pacios, Matthias F. Kramer, Bart R. Blokhuis, Alessandro Fiocchi, Sheriene Moussa Afify, Sebastian A. Jensen, Sonja Guethoff, Frank A. Redegeld, Isabella Pali-Schöll, Afd Pharmacology, Pharmacology, Biomedical International R+D GmbH, Austrian Science Fund, Bencard Allergie GmbH, Afify, Sheriene Moussa, Pacios, Luis F, Redegeld, Frank A, Pali-Schöll, Isabella, Hufnagl, Karin, Bianchini, Rodolfo, Guethoff, Sonja, Kramer, Matthias F, Fiocchi, Alessandro, Dvorak, Zdenek, Jensen-Jarolim, Erika, Roth-Walter, Franziska, Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank A [0000-0001-8830-7960], Pali-Schöll, Isabella [0000-0003-2089-6011], Hufnagl, Karin [0000-0002-2288-2468], Bianchini, Rodolfo [0000-0003-0351-6937], Guethoff, Sonja [0000-0001-5846-1035], Kramer, Matthias F [0000-0002-3740-4733], Fiocchi, Alessandro [0000-0002-2549-0523], Dvorak, Zdenek [0000-0002-3938-3585], Jensen-Jarolim, Erika [0000-0003-4019-5765], and Roth-Walter, Franziska [0000-0001-5005-9228]

Subjects
Farms, T cell, Antigen presentation, Immunology, Lactoglobulins, Immunoglobulin E, immunomodulation, BALB/c, Mice, Immune system, medicine, Animals, Humans, Immunology and Allergy, Antigen-presenting cell, immune resilience, Mice, Inbred BALB C, biology, beta-lactoglobulin, farm effect, Chemistry, Degranulation, holoBLG lozenge, Allergens, biology.organism_classification, medicine.anatomical_structure, food for special medical purposes FSMP, Dietary Supplements, biology.protein, Milk Hypersensitivity, Lozenge
Abstract

16 Pág., Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model., The study was supported by Biomedical International R+D GmbH, Vienna, Austria and Bencard Allergie GmbH, Munich, Germany and in part by the Austrian Science Fund FWF, grant SFB F4606-B28.

Published
2022

14. Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect

Author

Pali-Schöll, Isabella, Bianchini, Rodolfo, Afify, Sheriene Moussa, Hofstetter, Gerlinde, Winkler, Simona, Ahlers, Stella, Altemeier, Theresa, Mayerhofer, Hanna, Hufnagl, Karin, Korath, Anna D J, Pranger, Christina, Widhalm, Raimund, Hann, Stephan, Wittek, Thomas, Kasper-Giebl, Anne, Pacios, Luis F, Roth-Walter, Franziska, Vercelli, Donata, von Mutius, Erika, Jensen-Jarolim, Erika, Austrian Science Fund, Biomedical International R+D GmbH, Bencard Allergie GmbH, Pali-Schöll, Isabella [0000-0003-2089-6011], Bianchini, Rodolfo [0000-0003-0351-6937], Afify, Sheriene Moussa [0000-0003-2082-9038], Hofstetter, Gerlinde [0000-0003-2077-4479], Mayerhofer, Hanna [0000-0001-7973-2092], Hufnagl, Karin [0000-0002-2288-2468], Korath, Anna D J [0000-0002-6408-4157], Pranger, Christina [0000-0002-4232-5730], Widhalm, Raimund [0000-0002-8257-9903], Hann, Stephan [0000-0001-5045-7293], Wittek, Thomas [0000-0001-6113-8458], Kasper-Giebl, Anne [0000-0003-2736-2880], Pacios, Luis F [0000-0002-0585-4289], Roth-Walter, Franziska [0000-0001-5005-9228], Vercelli, Donata [0000-0001-5276-8976], von Mutius, Erika [0000-0002-8893-4515], Jensen-Jarolim, Erika [0000-0003-4019-5765], Pali-Schöll, Isabella, Bianchini, Rodolfo, Afify, Sheriene Moussa, Hofstetter, Gerlinde, Mayerhofer, Hanna, Hufnagl, Karin, Korath, Anna D J, Pranger, Christina, Widhalm, Raimund, Hann, Stephan, Wittek, Thomas, Kasper-Giebl, Anne, Pacios, Luis F, Roth-Walter, Franziska, Vercelli, Donata, von Mutius, Erika, and Jensen-Jarolim, Erika

Subjects
BLG, Immunomodulation, Zinc, Farm effect, Cattle, Stable
Abstract

15 Pág., Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle-specific protein as active component in this farm effect., This study was supported by the Austrian Science Fund FWF (SFB F4606-B28 and MCCA W1248-B30 to EJJ), in part by Biomedical International R+D GmbH, Vienna, Austria, and by Bencard Allergie GmbH, Munich, Germany.

Published
2022

15. Cow's milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells

Author

Alessandro Fiocchi, Frank A. Redegeld, Andreas Regner, Eva Untersmayr, Luis F. Pacios, Erika Jensen-Jarolim, Bart R. Blokhuis, Zdenek Dvorak, Karin Hufnagl, Lisa-Marie Petje, Isabella Pali-Schöll, Sheriene Moussa Afify, Franziska Roth-Walter, Austrian Science Fund, Biomedical International R+D GmbH, Bencard Allergie GmbH, Ministry of Higher Education & Scientific Research (Egypt), Roth-Walter, Franziska [0000-0001-5005-9228], Afify, Sheriene Moussa [0000-0003-2082-9038], Pacios, Luis F [0000-0002-0585-4289], Redegeld, Frank [0000-0001-8830-7960], Fiocchi, Alessandro [0000-0002-2549-0523], Untersmayr, Eva [0000-0002-1963-499X], Hufnagl, Karin [0000-0002-2288-2468], Pali-Schöll, Isabella [0000-0003-2089-6011], Jensen-Jarolim, Erika [0000-0003-4019-5765], Roth-Walter, Franziska, Afify, Sheriene Moussa, Pacios, Luis F, Redegeld, Frank, Fiocchi, Alessandro, Untersmayr, Eva, Hufnagl, Karin, Pali-Schöll, Isabella, Jensen-Jarolim, Erika, Afd Pharmacology, and Pharmacology

Subjects
0301 basic medicine, Allergy, Milk allergy, Lipocalin, Lactoglobulins, Immunoglobulin E, ligand, quercetin, Allergic sensitization, Mice, 0302 clinical medicine, iron, Immunology and Allergy, Mast Cells, Cow's milk, Mice, Inbred BALB C, milk, tolerance, biology, Chemistry, Allergen, Degranulation, Mast cell, BLG, Interleukin 10, medicine.anatomical_structure, Milk, Quercetin, lipocalin, Iron, Antigen presentation, Immunology, Ligand, β-lactoglobulin, 03 medical and health sciences, Immune system, medicine, Animals, Humans, medicine.disease, allergy, Bos d 5, cow's milk, 030104 developmental biology, 030228 respiratory system, biology.protein, Leukocytes, Mononuclear, Cattle, Milk Hypersensitivity, Tolerance
Abstract

Departamento de Biotecnología (INIA), Beta-lactoglobulin (BLG) is a bovine lipocalin in milk with an innate defense function. The circumstances under which BLG is associated with tolerance of or allergy to milk are not understood., Supported by the Austrian Science Fund FWF (grant SFB F4606-B28 ) and in part by Biomedical International R+D GmbH, Vienna, Austria, and by Bencard Allergie GmbH, Munich, Germany. S.M.A. was supported by a grant from the Egyptian Ministry of Higher Education ., 18 Pág.

Published
2021

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