Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/18219
Type
ArticleCopyright
Restricted access
Embargo date
2030-01-01
Collections
- IOC - Artigos de Periódicos [12642]
Metadata
Show full item record
STRUCTURAL AND DYNAMIC INSIGHTS INTO THE C-TERMINAL EXTENSION OF CYSTEINE PROTEINASE B FROM LEISHMANIA AMAZONENSIS
Extensão C-terminal de cisteína
Leishmania amazonensis
Predição da estrutura protéica
Dinâmica Molecular
proteinase B
Leishmania amazonensis
Protein structure prediction
Molecular dynamics
Author
Affilliation
Fundação Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica. 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. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica. 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. Rio de Janeiro, RJ. Brasil.
Abstract
Cysteine proteinase B (CPB) is a significant virulence factor for Leishmania infections. Upon processing from its zymogen form, it happens a release of the immunomodulatory CPB C-terminal extension (cyspep) into the cytoplasm of the macrophage. Epitopes derived from this fragment were shown to influence the proportion of lymphocytes CD8+ upon infection, favoring the parasite escaping from the host́s immune system. At present, there is no available structural data of cyspep, which impairs a proper understanding of its biological functions. Here, we attempted to build molecular models for this fragment and subsequently evaluate their stabilities in aqueous solution from molecular dynamics simulations analysis. Characterization of our models obtained with distinct techniques (comparative modeling, threading, and ab initio) indicates a prevalence of β-sheets in agreement with consensus secondary structure predictions. Simulation data supported this finding since the formation of new strands, along with a rapid disruption of helical content, were observed. Overall, this study provides a rationalization of epitope mapping data and an improved understanding of cyspep antigenicity.
Keywords in Portuguese
Proteinase BExtensão C-terminal de cisteína
Leishmania amazonensis
Predição da estrutura protéica
Dinâmica Molecular
Keywords
C-Terminal extension of cysteineproteinase B
Leishmania amazonensis
Protein structure prediction
Molecular dynamics
Share