Structure / function relationship of the Hsp40s.

• Grant number: 19/16114-1
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2019
• Effective date (End): October 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal researcher: Carlos Henrique Inacio Ramos
• Grantee: Carolina Oliveira Matos
• Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis, AP.TEM

Abstract

Co-chaperones of the Hsp40 (or DnaJ) family play a key role in the maintenance of proteostasis. The main functions are: 1) recognition and binding of partially folded proteins; 2) delivering these proteins to Hsp70, which aid in folding; and 3) concomitant stimulation of ATPase activity of Hsp70. Because they are involved in recognizing several different proteins, there are more representatives of Hsp40 in the cell than representatives of Hsp70, and the number and diversity of these co-chaperones increase with the complexity of the organism (only one in E. coli, two in yeast and more than 40 in humans and plants). In humans, some of these Hsp40 are involved in diseases and therefore studies related to the structure relationship of this co-chaperone have been increasing. We have already identified and characterized two of these co-chaperones in humans and two of yeast. We now intend to invest in the structural resolution of these proteins, what is challenging since co-chaperones from the Hsp40 family are dimeric, where the monomer is approximately 40 kDa and has an unstructured domain rich in glycines. To investigate the structure of this co-chaperones we have established a collaboration to use NMR in this strategy. Previous results on conformation and dynamics indicate that the strategy has the potential to generate the three-dimensional structure of domains and information about the relationship between them. With these results we will elaborate new strategies to determine the conformation of the dimer.