The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating.

ABSTRACT: Inactivation of voltage-gated calcium channels is crucial for the spatiotemporal coordination of calcium signals and prevention of toxic calcium buildup. Only one member of the highly conserved family of calcium channel beta-subunits--Ca(V)beta--inhibits inactivation. This unique property has been attributed to short variable regions of the protein; however, here we report that this inhibition actually is conferred by a conserved guanylate kinase (GK) domain and, moreover, that this domain alone recapitulates Ca(V)beta-mediated modulation of channel activation. We expressed and refolded the GK domain of Ca(V)beta(2a), the unique variant that inhibits inactivation, and of Ca(V)beta(1b), an isoform that facilitates it. The refolded domains of both Ca(V)beta variants were found to inhibit ina

SUBMITTER: Gonzalez-Gutierrez G 

PROVIDER: S-EPMC2544601 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature