Functional and structural characterization of Hsp110, a nucleotide exchange factor of the molecular chaperone Hsp70

• Applicant: Dr. Andreas Bracher
• Subject Area: Biochemistry
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 45728672

The molecular chaperone Hsp70 is a central component of the cellular protein folding and quality control machinery. Its interaction cycle with non-native protein substrate is regulated by the N-terminal ATPase domain, which itself is subject to regulation by cochaperones. Among these, nucleotide exchange factors drive the cycle forward by catalyzing the release of nucleotide. In eukaryotes, three diverging classes of nucleotide exchange factors exist in the cytosol and endoplasmic reticulum: BAG domain proteins, HspBP1/Fes1, and Hsp110/Hsp170 homologs. Our aim is to elucidate the mechanism by which Hsp110/Hsp170 homologs catalyze nucleotide exchange by a combined functional and structural approach. Using the cytosolic homologs, human Hsp110/Hsp70 and Sse1p/Ssb1p of Saccharomyces cerevisiae, as model systems, we plan to solve the crystal structure of a functional complex by X-ray diffraction. Ultimately, we wish to understand the structural basis for Hsp110-mediated nucleotide exchange and how Hsp110 and Hsp70 cooperate in protein folding.

• DFG Programme: Research Grants