7vfs

Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, apo state

spinqualitylabelsall models 7vfs, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7vfs 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 2.8Å Ligands: BMA, CA, NAG, PT5, R16, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CACB1_HUMAN Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:15615847, PubMed:8107964). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964).[UniProtKB:P19517] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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