The Molecular Mechanism of Hsp90’s Chaperone Activity

Hsp90 is a ubiquitous molecular chaperone that plays a role in both general protein folding as well as in the function of several intracellular signaling proteins such as the estrogen and glucocortocoid receptors, numerous serine/threonine and tyrosine kinases, and nitiric oxide synthase. We have recently solved the structure of the intact E. coli family member (HtpG) in both the apo and ADP-bound form, which provides a framework upon which more detailed mechanistic studies of Hsp90 can begin. I hope to understand at the atomic level how Hsp90 and the bacterial homolog, HtpG, functions as a molecular chaperone by trying to understand its interactions with client proteins and how its gross structural rearrangements contribute to its activity. This will be done using a variety of biophysical techniques such as fluorescence, x-ray crystallography, and in vivo crosslinking as well as the use of several enzymatic assays.

Publications:

Rouhani S, Facciotti MT, Woodcock G, Cheung V, Cunningham C, Nguyen D, Rad B, Lin CT, Lunde CS, and Glaeser RM. Crystallization of membrane proteins from media composed of connected-bilayer gels. Biopolymers. 2002;66(5):300-16.