Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/16504
Title: Exploring the unbinding of Leishmania (L.) amazonensis CPB derived-epitopes from H2 MHC class I protein
Authors: Brandt, Artur M. L.
Batista, Paulo Ricardo
Silva, Franklin Souza
Alves, Carlos Roberto
Caffarena, Ernesto Raul
Affilliation: Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil / Faculdade de Educação Tecnológica do Estado do Rio de Janeiro (FAETERJ). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil
Abstract: New strategies to control Leishmania disease demand an extensive knowledge about several aspects of infection including the understanding of its molecular events. In murine models, cysteine proteinase B from Leishmania amazonensis promotes regulation of immune response, and fragments from its C-terminus extension (cyspep) can play a decisive role in the hostparasite interaction. The interaction between cyspep-derived peptides and major histocompatibility complex (MHC) proteins is a crucial factor in Leishmania infections. Seven cyspep-derived peptides, previously identified as capable of interacting with H-2 (murine) MHC class I proteins, were studied in this work. We established a protocol to simulate the unbinding of these peptides from the cleft of H-2 receptors. From the simulations, we estimated the corresponding free energy of dissociation (DGd) and described the molecular events that occur during the exit of peptides from the cleft. To test the reliability of this method, we first applied it to a calibration set of four crystallographic MHC/peptide complexes. Next, we explored the unbinding of the seven complexes mentioned above. Results were consistent with DGd values obtained from surface plasmon resonance (SPR) experiments. We also identified some of the primary interactions between peptides and H-2 receptors, and we detected three regions of influence for the interaction. This pattern was systematically observed for the peptides and helped determine a minimum distance for the real interaction between peptides and H-2 proteins occurring at ~25 A ˚.
Keywords: Leishmania (Leishmania) amazonensis
free energy surface
H-2 Db
H-2 Kd
H-2 Kk and H-2 Ld haplotypes
immunological epitopes
metadynamics
keywords: Epitopo imunológico
Leishmania amazonensis
Superfície de energia livre
Metadinâmica
Issue Date: 2016
Publisher: Wiley
Citation: BRANDT, Artur M. L. et al. Exploring the unbinding of Leishmania (L.) amazonensis CPB derived-epitopes from H2 MHC class I proteins. Proteins, v.84, p.473-487, 2016.
DOI: 10.1002/prot.2499
ISSN: 0887-3583
Copyright: restricted access
Appears in Collections:Presidência Fiocruz – Artigos de Periódicos
IOC - Artigos de Periódicos

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