Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway.

Supporting Information Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway

Crosstalk between the Arg/N-end and Ac/N-end rule

Protein degradation in eukaryotic cells is mediated mainly by the ubiquitin (Ub)-proteasome system. One fundamental question in this field is about specific features in a protein that trigger its ubiquitylation and subsequent proteasomal degradation? In other words, the problem of degradation signals (degrons). The first degradation signals to be identified were N-degrons, which comprised desta...

Structural Bioinformatics and Protein Docking Analysis of the Molecular Chaperone-Kinase Interactions: Towards Allosteric Inhibition of Protein Kinases by Targeting the Hsp90-Cdc37 Chaperone Machinery

A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of protein kinase clients and supporting kinase functional activity is essential for the integrity and viability of signaling pathways involved in cell cycle control and organism development. Despite significant advances in understanding structure and function of molecular chaperones, the molecular mechanisms and gui...

Dynamics of the regulation of Hsp90 by the co-chaperone Sti1.

In eukaryotic cells, Hsp90 chaperones assist late folding steps of many regulatory protein clients by a complex ATPase cycle. Binding of clients to Hsp90 requires prior interaction with Hsp70 and a transfer reaction that is mediated by the co-chaperone Sti1/Hop. Sti1 furthers client transfer by inhibiting Hsp90's ATPase activity. To better understand how Sti1 prepares Hsp90 for client acceptanc...

The Mechanism of Hsp90 Regulation by the Protein Kinase-Specific Cochaperone p50cdc37

Recruitment of protein kinase clients to the Hsp90 chaperone involves the cochaperone p50(cdc37) acting as a scaffold, binding protein kinases via its N-terminal domain and Hsp90 via its C-terminal region. p50(cdc37) also has a regulatory activity, arresting Hsp90's ATPase cycle during client-protein loading. We have localized the binding site for p50(cdc37) to the N-terminal nucleotide binding...