Protein folding, stability and structure

• Grant number: 05/00462-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2006
• End date: September 30, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Carlos Henrique Inacio Ramos
• Grantee: Carlos Henrique Inacio Ramos
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 11/51534-0 - Functional and biophysical studies for LaSir2RP1, sirtuin of Leishmania amazonensis, BP.PD

Abstract

Our yet little understanding of the protein folding process holds back the understanding of several cellular processes because the conversion of a backbone into a native protein is a key element in the translation of organism's genetic information. As the organism ages, the folding seems to deviates becoming a signal to several diseases (mainly neurodegenerative). Protein misfolding causes deposition in the cell in the form of aggregates or amyloidal fibrils, both of which has toxic effects. One way to cell protection is throughout molecular chaperones, which help protein folding and may help protein disaggregation. Therefore, chaperones seem to have a fundamental role in the organism by increasing the success of physiological functions and protecting cells of become ill. My proposal has the main objective of understand protein folding by: 1) studying the folding pathway and the stability of proteins, mainly globins; 2) characterizing the forces and the mechanisms of amyloidal fibril formation; 3) structural and functional characterization of chaperones and 4) studying the mechanisms by which chaperones help folding, stop aggregation, ressolubilize aggregates, and interact with proteins involved in cell malignization. These phenomena mutually take place in the cell and their study in conjunction as proposed here may increase our understanding of protein folding inside the cell, which will generate important new thinking that lead to new therapies. (AU)