Identification of mitochondrial DUSPs ligands through bioinformatics tools

• Grant number: 21/10474-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2021
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Luciana Elena de Souza Fraga Machado
• Grantee: Luca Paulino Otvos
• 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 kinases and phosphatases are main actors in several signaling pathways and cellular functions, being responsible for the balance in the activation and production of molecules through the phosphorylation and dephosphorylation of their substrates. Different works have shown the importance of protein phosphatases located in sub-compartments of the mitochondria. Among them, DUSPs are tyrosine phosphatase proteins able to dephosphorylate their targets on serine, threonine, and tyrosine residues. Four DUSPs were identified in mitochondria: PTPMT1 (DUSP23), DUSP18, DUSP21, and DUSP26. So far, little, or no mitochondrial function has been unveiled for these DUSPs. Therefore, the objective of this work will be to investigate the ligands of these DUSPs within the mitochondria. Thus, we will perform a search for partners of mitochondrial DUSPs in silico and analyze these interactions to identify the cell signaling pathways that these DUSPs are involved. Finally, we will identify the interaction regions between PTPMT1 and two ligands. These results will make it possible to broaden the knowledge panorama about mitochondrial DUSPs, as well as guide future works that seek to deepen the characterization of the interactions and functions of these phosphatases. (AU)