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TitleMolecular insights into the gating mechanisms of voltage-gated calcium channel Ca2.3.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 516, Year 2023
Publish dateJan 31, 2023
AuthorsYiwei Gao / Shuai Xu / Xiaoli Cui / Hao Xu / Yunlong Qiu / Yiqing Wei / Yanli Dong / Boling Zhu / Chao Peng / Shiqi Liu / Xuejun Cai Zhang / Jianyuan Sun / Zhuo Huang / Yan Zhao /
PubMed AbstractHigh-voltage-activated R-type Ca2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we ...High-voltage-activated R-type Ca2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we determine the high-resolution cryo-electron microscopy (cryo-EM) structure of human Ca2.3 in complex with the α2δ1 and β1 subunits. The VSD is stabilized in the resting state. Electrophysiological experiments elucidate that the VSD is not required for channel activation, whereas the other VSDs are essential for channel opening. The intracellular gate is blocked by the W-helix. A pre-W-helix adjacent to the W-helix can significantly regulate closed-state inactivation (CSI) by modulating the association and dissociation of the W-helix with the gate. Electrostatic interactions formed between the negatively charged domain on S6, which is exclusively conserved in the Ca2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5 helix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of Ca2 channels.
External linksNat Commun / PubMed:36720859 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

33285

7xlq

EMDB-33285, PDB-7xlq:
Structure of human R-type voltage-gated CaV2.3-alpha2/delta1-beta1 channel complex in the ligand-free (apo) state
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-R16:
HEXADECANE / Hexadecane

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM / Phosphatidylethanolamine

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Voltage-gated calcium channel / CaV2.3 / Complex

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