1T0J

Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit

Summary for 1T0J

• Entry DOI: 10.2210/pdb1t0j/pdb
• Related: 1TOH
• Descriptor: voltage-gated calcium channel subunit beta2a, Voltage-dependent L-type calcium channel alpha-1C subunit, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: sh3 domain, nucleotide kinase like domain, ion channel, calcium channel, aid, signaling protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane, sarcolemma; Peripheral membrane protein; Cytoplasmic side: Q8VGC3 Q8VGC3; Membrane; Multi-pass membrane protein: Q13936
• Total number of polymer chains: 3
• Total formula weight: 42662.00

Authors

Van Petegem, F.,Clark, K.,Chatelain, F.,Minor Jr., D. (deposition date: 2004-04-09, release date: 2004-06-15, Last modification date: 2023-08-23)

Primary citation

Van Petegem, F.,Clark, K.A.,Chatelain, F.C.,Minor, D.L.
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.
Nature, 429:671-675, 2004

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.

PubMed: 15141227
DOI: 10.1038/nature02588

Experimental method

X-RAY DIFFRACTION (2 Å)