Molecular modeling of class I and II alleles of the major histocompatibility complex in <Emphasis Type="Italic">Salmo salar</Emphasis> |
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Authors: | Constanza Cárdenas Axel Bidon-Chanal Pablo Conejeros Gloria Arenas Sergio Marshall F Javier Luque |
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Institution: | 1.Laboratorio de Genética e Inmunología Molecular, Facultad de Ciencias,Pontificia Universidad Católica de Valparaíso, Chile,Valparaiso,Chile;2.Laboratorio de Genética e Inmunología Molecular, Instituto de Biología, Facultad de Ciencias,Pontificia Universidad Católica de Valparaíso, Chile,Valparaiso,Chile;3.NBC-Núcleo de Biotecnología Curauma, Campus Curauma PUCV,Valparaiso,Chile;4.Centro Regional Estudios Alimentación Saludable (CREAS),PUCV,Valparaiso,Chile;5.Departament de Fisicoquímica and Institut de Biomedicina (IBUB), Facultat de Farmàcia,Universitat de Barcelona,Barcelona,Spain |
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Abstract: | Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role
in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports
molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific
preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored
by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide
interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations.
The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the
binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both
class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural
models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific
interactions and to design vaccines against viral pathogens. |
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