Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.

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Citation

Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr

Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.

Nature. 2004 Jun 10;429(6992):671-5. Epub 2004 May 12.

PubMed ID
15141227 [ View in PubMed
]
Abstract

Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and neurotransmitter release, neuronal migration, activation of calcium-dependent signalling cascades, and synaptic input integration. An essential Ca(V) intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain (the alpha-interaction domain, AID) between transmembrane domains I and II of the pore-forming alpha(1) subunit and profoundly affects multiple channel properties such as voltage-dependent activation, inactivation rates, G-protein modulation, drug sensitivity and cell surface expression. Here, we report the high-resolution crystal structures of the Ca(V)beta2a conserved core, alone and in complex with the AID. Previous work suggested that a conserved region, the beta-interaction domain (BID), formed the AID-binding site; however, this region is largely buried in the Ca(V)beta core and is unavailable for protein-protein interactions. The structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages the AID through an extensive, conserved hydrophobic cleft (named the alpha-binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta near the intracellular end of a pore-lining segment, called IS6, that has a critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Voltage-dependent L-type calcium channel subunit alpha-1CQ13936Details