Structural highlights
4dey is a 2 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 1t3l, 4dex |
| Gene: | CACNA1C, CACH2, CACN2, CACNL1A1, CCHL1A1 (European rabbit), CACNB2, CACNLB2 (European rabbit) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CAC1C_RABIT] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function (By similarity). [CACB2_RABIT] The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Publication Abstract from PubMed
Voltage-dependent calcium channels (VDCCs) allow the passage of Ca(2+) ions through cellular membranes in response to membrane depolarization. The channel pore-forming subunit, alpha1, and a regulatory subunit (Ca(V)beta) form a high affinity complex where Ca(V)beta binds to a alpha1 interacting domain in the intracellular linker between alpha1 membrane domains I and II (I-II linker). We determined crystal structures of Ca(V)beta2 functional core in complex with the Ca(V)1.2 and Ca(V)2.2 I-II linkers to a resolution of 1.95 and 2.0 A, respectively. Structural differences between the highly conserved linkers, important for coupling Ca(V)beta to the channel pore, guided mechanistic functional studies. Electrophysiological measurements point to the importance of differing linker structure in both Ca(V)1 and 2 subtypes with mutations affecting both voltage- and calcium-dependent inactivation and voltage dependence of activation. These linker effects persist in the absence of Ca(V)beta, pointing to the intrinsic role of the linker in VDCC function and suggesting that I-II linker structure can serve as a brake during inactivation.
The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.,Almagor L, Chomsky-Hecht O, Ben-Mocha A, Hendin-Barak D, Dascal N, Hirsch JA J Neurosci. 2012 May 30;32(22):7602-13. PMID:22649239[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Almagor L, Chomsky-Hecht O, Ben-Mocha A, Hendin-Barak D, Dascal N, Hirsch JA. The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis. J Neurosci. 2012 May 30;32(22):7602-13. PMID:22649239 doi:10.1523/JNEUROSCI.5727-11.2012
