We investigate how chaperones shape the conformational landscape of signaling proteins during their maturation

Molecular chaperones are ubiquitous proteins that assist the de novo folding of nascent polypeptides. The heat shock protein 90 (Hsp90), in cohort with other proteins termed co-chaperones, forms a machinery that acts at a late stage of protein folding. It confers fine structural changes to its substrates and induces their conformational maturation to a stable, functional and active form. Its “clients” comprise a variety of proteins involved in diverse cellular processes from signal transduction, to telomere maintenance and protein trafficking. Cdc37 (cell division cycle, 37) is a gain-of-specificity co-chaperone of the Hsp90 machinery, specializing in the recruitment of protein kinases. Our long term goal is to understand the molecular mechanism by which different components of the Hsp90 machinery allow activation and afford stability of oncogenic kinases. We hope that our mechanistic studies will ultimately lead to novel routes for a pharmacologic intervention in cancer.

Keramisanou D, Aboalroub A, Zhang Z, Liu W, Marshall D, Diviney A, Larsen RW, Landgraf R, Gelis I., Molecular Mechanism of Protein Kinase Recognition and Sorting by the Hsp90 Kinome-Specific Cochaperone Cdc37.
Molecular Cell, 62, 260-271 (2016)