title: Structural and dynamic insights into the C-terminal extension of cysteine proteinase B from Leishmania amazonensis.
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.
authors.affiliation: Programa De Computação Científica (PROCC), Fundação Oswaldo Cruz, Manguinhos, Rio De Janeiro, RJ CEP 21040-360, Brazil.
authors.forename: Deborah Antunes
authors.initials: DA
authors.lastname: Santos
authors.affiliation: Programa De Computação Científica (PROCC), Fundação Oswaldo Cruz, Manguinhos, Rio De Janeiro, RJ CEP 21040-360, Brazil.
authors.forename: Mauricio Garcia
authors.initials: MG
authors.lastname: de Souza Costa
authors.affiliation: Laboratório De Biologia Molecular E Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio De Janeiro, RJ CEP 21040-360, Brazil.
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Alves
authors.affiliation: Programa De Computação Científica (PROCC), Fundação Oswaldo Cruz, Manguinhos, Rio De Janeiro, RJ CEP 21040-360, Brazil. Electronic address: ernesto.caffarena@fiocruz.br.
authors.forename: Ernesto Raul
authors.initials: ER
authors.lastname: Caffarena
mesh_terms: D000595:Amino Acid Sequence; D057056:Cysteine Proteases / Q000737:chemistry*; D004220:Disulfides / Q000378:metabolism; D007891:Leishmania / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D012996:Solutions; D013997:Time Factors
chemical_list: D004220:Disulfides; D015800:Protozoan Proteins; D012996:Solutions; D057056:Cysteine Proteases
keywords: C-Terminal extension of cysteine proteinase B; Leishmania amazonensis; Molecular dynamics; Protein structure prediction