Exploration of the Binding Preferences of HOP from Aedes aegypti and Homo sapiens

• Grant number: 25/06003-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2025
• End date: July 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Henrique Inacio Ramos
• Grantee: Albert Leder St John
• Supervisor: Jason e Gestwicki
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of California, San Francisco (UCSF), United States
• Associated to the scholarship: 23/16667-6 - Unraveling the Relationship Between Heat Shock Proteins (HSPs) and HSP90 in Aedes aegypti. Comprehensive Investigation of the Chaperones HSF, HOP, and TRAP1a, BP.DR

Abstract

Carboxylate clamp tetracopeptide repeat (CC-TPR) proteins, e.g., HSP70-HSP90 organizing protein (HOP), protein phosphatase 5 (PP5) and carboxy-terminus of HSP70 interacting protein (CHIP), are cochaperones that interact with cytosolic HSP70 and HSP90 through a conserved EEVD motif at their C-terminus. Recent research from Professor Jason Gestwicki's laboratory has identified optimized EEVD-like motif sequences and demonstrated the binding of non-chaperone proteins to PP5 and CHIP, expanding our understanding of their functional roles. This study plans to develop optimized EEVD-like motifs for HOP Aedes aegypti (AaHOP) and Homo sapiens (HsHOP), which possess two and three CC-TPR domains, respectively. For the methodology, a positional scanning synthetic combinatorial library (PSSCL) of five amino acid peptide will be synthesized and their interaction with HOP will be analyzed using differential scanning fluorimetry (DSF), fluorescence polarization (FP) and competitive chemoproteomics assays. These findings will contribute to the design of inhibitors against HOP of different species, offering potential therapeutic agents for Aedes aegypti-borne diseases, and identification of putative interactors of HOP. (AU)