7XLQ

Structure of human R-type voltage-gated CaV2.3-alpha2/delta1-beta1 channel complex in the ligand-free (apo) state

Summary for 7XLQ

• Entry DOI: 10.2210/pdb7xlq/pdb
• EMDB information: 33285
• Descriptor: Voltage-dependent R-type calcium channel subunit alpha-1E, 2-acetamido-2-deoxy-beta-D-glucopyranose, Voltage-dependent calcium channel subunit alpha-2/delta-1, ... (10 entities in total)
• Functional Keywords: voltage-gated calcium channel, cav2.3, complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 458752.88

Authors

Gao, Y.,Qiu, Y.,Wei, Y.,Dong, Y.,Zhang, X.C.,Zhao, Y. (deposition date: 2022-04-22, release date: 2023-02-08, Last modification date: 2024-11-20)

Primary citation

Gao, Y.,Xu, S.,Cui, X.,Xu, H.,Qiu, Y.,Wei, Y.,Dong, Y.,Zhu, B.,Peng, C.,Liu, S.,Zhang, X.C.,Sun, J.,Huang, Z.,Zhao, Y.
Molecular insights into the gating mechanisms of voltage-gated calcium channel Ca V 2.3.
Nat Commun, 14:516-516, 2023

PubMed Abstract: 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.

PubMed: 36720859
DOI: 10.1038/s41467-023-36260-2

Experimental method

ELECTRON MICROSCOPY (3.1 Å)