2NCA: Structural Model for the N-terminal Domain of Human Cdc37

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.
PDB ID: 2NCADownload
MMDB ID: 138741
PDB Deposition Date: 2016/3/23
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2NCA: monomeric; determined by author
Molecular Components in 2NCA
Label Count Molecule
Protein (1 molecule)
Hsp90 Co-chaperone Cdc37(Gene symbol: CDC37)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB