A03 Buchner/Sattler: Conformational regulation of the Hsp90 machinery
The chaperone Hsp90 undergoes large ATP-induced conformational changes. This conformational cycle is regulated by co-chaperones and posttranslational modifications.We employ an integrated biochemical, biophysical and structural approach to obtain mechanistic insight in the regulation of Hsp90 activity and the processing of client proteins. NMR, SAXS, H/DX coupled to mass spectrometry and FRET are used to study the conformational cycle of Hsp90 and its response to nucleotide and co-chaperone binding. Furthermore, the structures as well as mechanisms of Hsp90 co-chaperones and the principles of Hsp90-client interactions will be determined.