Analysis of the ligands and the interaction network of the mitochondrial protein phosphatase PGAM5

• Grant number: 22/02313-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2022
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Luciana Elena de Souza Fraga Machado
• Grantee: Sofia de Oliveira Farias
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/02605-3 - Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology, AP.JP

Abstract

Protein dephosphorylation of protein phosphatases is a post-translational modification essential for cellular maintenance and regulatory processes. These enzymes can dephosphorylate tyrosine or serine/threonine residues dependent on nucleophilic residues such as cysteine, aspartate, or histidine. Protein phosphatases are located in different cellular compartments such as mitochondria. However, very little is still known about mitochondrial protein phosphatases. Among the mitochondrial protein phosphatases, the histidine-dependent serine-threonine phosphatase protein, called protein phosphoglycerate mutase 5 (PGAM5) stands out, which has been described in cellular apoptosis processes. Thus, we intend to analyze the possible ligands and cell signaling pathways in that the mitochondrial protein phosphatase PGAM5 is involved. In this way, a bioinformatical analysis will be carried out to identify PGAM5 ligands and the cellular signaling. Following, in vitro experiments will be performed to analyze the interaction between PGAM5 and two ligands throughout pull-down experiments. After analyzing the interaction between the proteins, it will be characterized the interaction motif with the goal to identify new ligands. (AU)