Mem Inst Oswaldo Cruz, Rio de Janeiro, 112(9) September 2017
Original Article

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

Amanda Sutter1, Deborah Antunes1, Mariana Silva-Almeida2, Maurício Garcia de Souza Costa1, Ernesto Raul Caffarena1,+

1Grupo de Biofísica Computacional e Modelagem Molecular, Programa de Computação Científica, Rio de Janeiro, RJ, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro, RJ, Brasil

Page: 617-625 DOI: 10.1590/0074-02760160522
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ABSTRACT

BACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the infection of promastigotes and resistance to hostu2019s 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.

Financial support: FAPERJ, CNPq, CAPES.
ERC is a fellow researcher at the CNPq
+ Corresponding author: ernesto.caffarena@fiocruz.br
Received 5 December 2016
Accepted 2 February 2017

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