| Structural highlights
7vfv is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 3Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CAC1B_HUMAN 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-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Publication Abstract from PubMed
N-type voltage-gated calcium (Ca(V)) channels mediate Ca(2+) influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human Ca(V)2.2 complex in apo, ziconotide-bound, and two Ca(V)2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP(2)) molecule, which is distinct from the other three VSDs of Ca(V)2.2, as well as activated VSDs observed in previous structures of Ca(V) channels. This structure reveals the molecular basis for the unique inactivation process of Ca(V)2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain.
Closed-state inactivation and pore-blocker modulation mechanisms of human Ca(V)2.2.,Dong Y, Gao Y, Xu S, Wang Y, Yu Z, Li Y, Li B, Yuan T, Yang B, Zhang XC, Jiang D, Huang Z, Zhao Y Cell Rep. 2021 Nov 2;37(5):109931. doi: 10.1016/j.celrep.2021.109931. PMID:34731621[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dong Y, Gao Y, Xu S, Wang Y, Yu Z, Li Y, Li B, Yuan T, Yang B, Zhang XC, Jiang D, Huang Z, Zhao Y. Closed-state inactivation and pore-blocker modulation mechanisms of human Ca(V)2.2. Cell Rep. 2021 Nov 2;37(5):109931. PMID:34731621 doi:10.1016/j.celrep.2021.109931
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