Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis

BACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the infection of promastigotes and resistance to host’s defenses. Leishmania (Viannia) braziliensis contains several leishmanolysin genes in its genome, especially in chromosome 10. Howe...

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Main Authors: Amanda Sutter, Deborah Antunes, Mariana Silva-Almeida, Maurício Garcia de Souza Costa, Ernesto Raul Caffarena
Format: Article
Language:English
Published: Fundação Oswaldo Cruz (FIOCRUZ)
Series:Memorias do Instituto Oswaldo Cruz
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762017000900617&lng=en&tlng=en
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author Amanda Sutter
Deborah Antunes
Mariana Silva-Almeida
Maurício Garcia de Souza Costa
Ernesto Raul Caffarena
author_facet Amanda Sutter
Deborah Antunes
Mariana Silva-Almeida
Maurício Garcia de Souza Costa
Ernesto Raul Caffarena
author_sort Amanda Sutter
collection DOAJ
description BACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the infection of promastigotes and resistance to host’s defenses. Leishmania (Viannia) braziliensis contains several leishmanolysin genes in its genome, especially in chromosome 10. However, the functional impact of such diversity is not understood, but may be attributed partially to the lack of structural data for proteins from this parasite. OBJECTIVES This works aims to compare leishmanolysin sequences from L. (V.) braziliensis and to understand how the diversity impacts in their structural and dynamic features. METHODS Leishmanolysin sequences were retrieved from GeneDB. Subsequently, 3D models were built using comparative modeling methods and their dynamical behavior was studied using molecular dynamic simulations. FINDINGS We identified three subgroups of leishmanolysins according to sequence variations. These differences directly affect the electrostatic properties of leishmanolysins and the geometry of their active sites. We identified two levels of structural heterogeneity that might be related to the ability of promastigotes to interact with a broad range of substrates. MAIN CONCLUSION Altogether, the structural plasticity of leishmanolysins may constitute an important evolutionary adaptation rarely explored when considering the virulence of L. (V.) braziliensis parasites.
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spelling doaj.art-270a4e50b2fe4267a687246dd1c4be172023-09-02T22:14:57ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-8060112961762510.1590/0074-02760160522S0074-02762017000900617Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensisAmanda SutterDeborah AntunesMariana Silva-AlmeidaMaurício Garcia de Souza CostaErnesto Raul CaffarenaBACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the infection of promastigotes and resistance to host’s defenses. Leishmania (Viannia) braziliensis contains several leishmanolysin genes in its genome, especially in chromosome 10. However, the functional impact of such diversity is not understood, but may be attributed partially to the lack of structural data for proteins from this parasite. OBJECTIVES This works aims to compare leishmanolysin sequences from L. (V.) braziliensis and to understand how the diversity impacts in their structural and dynamic features. METHODS Leishmanolysin sequences were retrieved from GeneDB. Subsequently, 3D models were built using comparative modeling methods and their dynamical behavior was studied using molecular dynamic simulations. FINDINGS We identified three subgroups of leishmanolysins according to sequence variations. These differences directly affect the electrostatic properties of leishmanolysins and the geometry of their active sites. We identified two levels of structural heterogeneity that might be related to the ability of promastigotes to interact with a broad range of substrates. MAIN CONCLUSION Altogether, the structural plasticity of leishmanolysins may constitute an important evolutionary adaptation rarely explored when considering the virulence of L. (V.) braziliensis parasites.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762017000900617&lng=en&tlng=enLeishmania sppLeishmania (Viannia) braziliensismetalloproteasesleishmanolysinscomparative modelingmolecular dynamics
spellingShingle Amanda Sutter
Deborah Antunes
Mariana Silva-Almeida
Maurício Garcia de Souza Costa
Ernesto Raul Caffarena
Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
Memorias do Instituto Oswaldo Cruz
Leishmania spp
Leishmania (Viannia) braziliensis
metalloproteases
leishmanolysins
comparative modeling
molecular dynamics
title Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
title_full Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
title_fullStr Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
title_full_unstemmed Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
title_short Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
title_sort structural insights into leishmanolysins encoded on chromosome 10 of leishmania viannia braziliensis
topic Leishmania spp
Leishmania (Viannia) braziliensis
metalloproteases
leishmanolysins
comparative modeling
molecular dynamics
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762017000900617&lng=en&tlng=en
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