Conformational and functional characterization of Aedes aegypti Hsp70 chaperone

• Grant number: 20/11645-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: September 30, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Henrique Inacio Ramos
• Grantee: Claudia de Lourenço
• Host 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

For a protein to perform its functions, it must be in its folded state, which is soluble and functional. The folding process can be affected by several circumstances, such as the high concentration of macromolecules in the medium, the change in pH and the increase in temperature. Therefore, many proteins need help to bind, and this help is provided by molecular chaperones and Hsps ('heat shock proteins'), such as those that form the Hsp70 complex (Hsp70 / Hsp40 / GrpE). In this complex, Hsp40, a 'holder', recognizes partially folded proteins and delivers them to Hsp70, which has ATPasic activity and acts as an 'enovelase' helping both in the folding of new proteins and in the reactivation of protein clusters. The inhibition of this complex increases the cellular sensitivity to various types of stresses, while the overexpression of the system leads to an opposite and beneficial effect, even reverting phenotypes caused by amyloidogenesis. This project aims to expand our knowledge from the following specific objectives: 1) purification of the Hsp70 chaperone from Aedes aegypti, 2) characterization of its conformation, 3) evaluation of its ATPase activity and 4) evaluation of its chaperone activity. These studies have a high potential to solidify and increase our knowledge on the characteristics of the Hsp70 chaperone, in order to raise strategies to control the mosquito.