Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3

Yiwei 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 () and Yan Zhao ()
Additional contact information
Yiwei Gao: Chinese Academy of Sciences
Shuai Xu: Peking University Health Science Center
Xiaoli Cui: Chinese Academy of Sciences
Hao Xu: Chinese Academy of Sciences
Yunlong Qiu: Chinese Academy of Sciences
Yiqing Wei: Chinese Academy of Sciences
Yanli Dong: Chinese Academy of Sciences
Boling Zhu: Chinese Academy of Sciences
Chao Peng: Peking University Health Science Center
Shiqi Liu: Peking University Health Science Center
Xuejun Cai Zhang: Chinese Academy of Sciences
Jianyuan Sun: Chinese Academy of Sciences
Zhuo Huang: Peking University Health Science Center
Yan Zhao: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract High-voltage-activated R-type CaV2.3 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 CaV2.3 in complex with the α2δ1 and β1 subunits. The VSDII is stabilized in the resting state. Electrophysiological experiments elucidate that the VSDII 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 S6II, which is exclusively conserved in the CaV2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5II helix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of CaV2 channels.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36260-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36260-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36260-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().