Interactome of glyceraldehyde-3-phosphate dehydrogenase points to the existence of metabolons in Paracoccidioides lutzii
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2019
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Paracoccidioides is a dimorphic fungus, the causative agent of paracoccidioidomycosis.
The disease is endemic within Latin America and prevalent in Brazil. The treatment is
based on azoles, sulfonamides and amphotericin B. The seeking for new treatment
approaches is a real necessity for neglected infections. Glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) is an essential glycolytic enzyme, well known for its multitude
of functions within cells, therefore categorized as a moonlight protein. To our knowledge,
this is the first approach performed on the Paracoccidioides genus regarding the
description of PPIs having GAPDH as a target. Here, we show an overview of
experimental GAPDH interactome in different phases of Paracoccidioides lutzii and
an in silico analysis of 18 proteins partners. GAPDH interacted with 207 proteins in
P. lutzii. Several proteins bound to GAPDH in mycelium, transition and yeast phases
are common to important pathways such as glycolysis and TCA. We performed a
co-immunoprecipitation assay to validate the complex formed by GAPDH with triose
phosphate isomerase, enolase, isocitrate lyase and 2-methylcitrate synthase. We found
GAPDH participating in complexes with proteins of specific pathways, indicating the
existence of a glycolytic and a TCA metabolon in P. lutzii. GAPDH interacted with several
proteins that undergoes regulation by nitrosylation. In addition, we modeled the GAPDH
3-D structure, performed molecular dynamics and molecular docking in order to identify
the interacting interface between GAPDH and the interacting proteins. Despite the large
number of interacting proteins, GAPDH has only four main regions of contact with
interacting proteins, reflecting its ancestrality and conservation over evolution.
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GAPDH, Paracoccidioides, Protein-protein interaction, Metabolon, Interactome
Citação
SILVA, Kleber Santiago Freitas e et al. Interactome of glyceraldehyde-3-phosphate dehydrogenase points to the existence of metabolons in Paracoccidioides lutzii. Frontiers in Microbiology, Lausanne, v. 10, e1537, 2019. DOI: 10.3389/fmicb.2019.01537. Disponível em: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.01537/full. Acesso em: 22 nov. 2024.