2NCA

Structural Model for the N-terminal Domain of Human Cdc37

Summary for 2NCA

• Entry DOI: 10.2210/pdb2nca/pdb
• Related: 1US7 2K5B 2N5X
• NMR Information: BMRB: 26012
• Descriptor: Hsp90 co-chaperone Cdc37 (1 entity in total)
• Functional Keywords: chaperone, cochaperone
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q16543
• Total number of polymer chains: 1
• Total formula weight: 15407.26

Authors

Zhang, Z.,Keramisanou, D.,Gelis, I. (deposition date: 2016-03-23, release date: 2016-05-04, Last modification date: 2024-05-15)

Primary citation

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

PubMed Abstract: Despite the essential functions of Hsp90, little is known about the mechanism that controls substrate entry into its chaperone cycle. We show that the role of Cdc37 cochaperone reaches beyond that of an adaptor protein and find that it participates in the selective recruitment of only client kinases. Cdc37 recognizes kinase specificity determinants in both clients and nonclients and acts as a general kinase scanning factor. Kinase sorting within the client-to-nonclient continuum relies on the ability of Cdc37 to challenge the conformational stability of clients by locally unfolding them. This metastable conformational state has high affinity for Cdc37 and forms stable complexes through a multidomain cochaperone interface. The interaction with nonclients is not accompanied by conformational changes of the substrate and results in substrate dissociation. Collectively, Cdc37 performs a quality control of protein kinases, where induced conformational instability acts as a "flag" for Hsp90 dependence and stable cochaperone association.

PubMed: 27105117
DOI: 10.1016/j.molcel.2016.04.005

Experimental method

SOLUTION NMR