The chaperone heat shock protein 90 (Hsp90), is a large, dimeric ATP-driven molecular machine. It is essential in eukaryotes and is known to function as a part of many complexes. These complexes are involved, amongst other things, in the regulation of cell division and signalling . As such, Hsp90 has emerged as an important target for the development of cancer therapeutics .
Hsp90 is highly dynamic and flexible meaning that structural studies do not provide a full picture of the mechanisms by which it functions. Thus, despite the importance of this fascinating molecular machine, the exact way in which Hsp90 undergoes conformational changes, the roles of nucleotides, different domain orientations and how these influence the function of the chaperone in complex with its co-chaperones are not yet fully understood.
Using single molecule optical trapping, we have so far elucidated the mechanism by which this large protein folds , characterised the role of its flexible charged linker region , performed a detailed comparison of Hsp90 orthologues and homologues [5,6] and uncovered the role of nucleotide binding in the stability of the dimeric interface of Hsp90 . Our current research efforts are building on these findings to study the effect of co-chaperones on the conformational cycle and single molecule mechanics of Hsp90, extending this with the help of our new C-trap instrument.
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Instructor: Dr Kasia Tych
Duration: 1 hour
Cost: Free of charge