Structural basis of intracellular peptides-protein interactions

• Grant number: 19/07332-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2019
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Emer Suavinho Ferro
• Grantee: Carolina Angelica da Silva Parada
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides, AP.TEM

Abstract

Intracellular peptides are peptides that escape cytosolic proteolytic degradation, are not part of autoimmune recognition, and accumulate inside the cells. The majority of intracellular peptides has unknown functions. Recently, our group observed the presence of intracellular peptides on the structure of protein complexes available on Protein Data Bank (PDB). From 627 identified human peptides, 5286 structures are deposited as protein-protein complexes, where 48% display intracellular peptides on the interface of protein-protein interactions, suggesting that intracellular peptides are part of protein-protein interaction domains therefore may play an essencial biological role in the cells. The functions and the manner in which these peptide-protein interactions occur still need to be elucidated. The challenge of this project is to identify intracellular peptides of the human peptidome, develop and validate high-throughput experimental methods for characterization of free or complexed intracellular peptide structures and interactions in real time. For method optimization, we will use Hek-293 human cell lines and the VRD7 peptide, which is a fragment derived from the protein peptidil-prolil cys-trans isoisomerase (FKBP506-binding protein). The characterization of individual and global effects of intracellular peptides in protein-protein interactions will be tested by Nano Bit® and cross-linking-MS. The knowledge generated by this research could demonstrate the biological role of intracellular peptides as well as show their potential use as biopharmaceuticals for clinical application. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PARADA, CAROLINA A.; DE OLIVEIRA, IVAN PIRES; GEWEHR, MAYARA C. F.; MACHADO-NETO, JOAO AGOSTINHO; LIMA, KELI; EICHLER, ROSANGELA A. S.; LOPES, LUCIA R.; BECHARA, LUIZ R. G.; FERREIRA, JULIO C. B.; FESTUCCIA, WILLIAM T.; et al. ffect of FKBP12-Derived Intracellular Peptides on Rapamycin-Induced FKBP-FRB Interaction and Autophag. ELL, v. 11, n. 3, FEB 2022. (19/25049-9, 13/07937-8, 19/27149-0, 17/02201-4, 16/04000-3, 19/07332-5, 19/23864-7)

SAKAYA, GABRIEL R.; PARADA, CAROLINA A.; EICHLER, ROSANGELA A.; YAMAKI, VITOR N.; NAVON, AMI; HEIMANN, ANDREA S.; FIGUEIREDO, EBERVAL G.; FERRO, EMER S.. Peptidomic profiling of cerebrospinal fluid from patients with intracranial saccular aneurysms. JOURNAL OF PROTEOMICS, v. 240, MAY 30 2021. (16/04000-3, 19/07332-5)