Unraveling the Relationship Between Heat Shock Proteins (HSPs) and HSP90 in Aedes aegypti. Comprehensive Investigation of the Chaperones HSF, HOP, and TRAP1a

• Grant number: 23/16667-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: July 31, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Henrique Inacio Ramos
• Grantee: Albert Leder St John
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 25/06003-9 - Exploration of the Binding Preferences of HOP from Aedes aegypti and Homo sapiens, BE.EP.DR

Abstract

The regulation of cellular proteostasis, maintained by the protein quality control (PQC) system, is an intricate process involving the action of molecular chaperones, also known as HSPs (heat shock proteins), and the ubiquitin-proteasome system. These factors coordinate the synthesis, folding, maintenance of conformation, and degradation of polypeptide proteins. Imbalance in these factors can lead to the accumulation of non-functional proteins, resulting in severe consequences for cells, including cell death. Among the HSPs, HSP90 is one of the most important players involved in PQC, demonstrating interactions with over 10% of the cellular proteome in yeast. This project aims to complement an ongoing study, the primary objective of which is to establish a potential interactome of the HSP90 family in Aedes aegypti, as this is a crucial step in understanding the stress response process and identifying potential intervention targets. In the context of the ongoing study, the cytosolic HSP90 and HSP70 of this insect have been cloned and studied. This specific project aims to study the chaperones HSF, HOP, and TRPA1a, all related to HSP90. Recombinant proteins will be expressed, purified, and conformationally characterized using methods such as circular dichroism, analytical size-exclusion chromatography, SEC-MALS, DLS, and intrinsic fluorescence. Furthermore, functional characterization will be performed by investigating the expression of these proteins in mosquito larval cells, as well as their role as chaperones. Lastly, interactions between these proteins and other HSPs will be investigated. We anticipate that the characterization of these proteins will contribute to a better understanding of Aedes aegypti, a vector for various diseases, and enable the development of strategies to combat it.