Functional dissection of the intramolecular Src homology 3-guanylate kinase domain coupling in voltage-gated Ca2+ channel beta-subunits.

ABSTRACT: The beta-subunit of voltage-gated Ca(2+) channels is essential for trafficking the channels to the plasma membrane and regulating their gating. It contains a Src homology 3 (SH3) domain and a guanylate kinase (GK) domain, which interact intramolecularly. We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak SH3-GK interface and a direct connection of the SH3 and GK domains. Alterations of these elements uncouple the two functions of the beta-subunit, degrading its ability to regulate gating while leaving its chaperone effect intact.

SUBMITTER: Chen YH 

PROVIDER: S-EPMC2739582 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature