Phosphorylated and unphosphorylated serine 13 of CDC37 stabilize distinct interactions between its client and HSP90 binding domains.

ABSTRACT: Folding and maturation of most protein kinases require chaperone assistance. In higher eukaryotes, CDC37 is the predominant cochaperone that facilitates the transfer of kinase clients to HSP90. Kinase recognition is thought to occur through the N-terminal domain, which has, thus far, eluded structure determination. Client processing also requires the phosphorylation of the N-terminal tail at Ser13 by protein kinase CK2 (casein kinase 2). How phosphorylation alters the molecular properties of CDC37 is not understood. We show that the phosphorylation at Ser13 induces a large shift toward a more compact structure, based on ANS fluorescence, while modestly increasing secondary structure. Moreover, this transition requires interactions of the N-terminal domain and the remainder of CDC37. The st

SUBMITTER: Liu W 

PROVIDER: S-EPMC4840409 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature