8WEA

Human L-type voltage-gated calcium channel Cav1.2 (Class II) in the presence of pinaverium at 3.2 Angstrom resolution

8WEA の概要

• エントリーDOI: 10.2210/pdb8wea/pdb
• EMDBエントリー: 37476
• 分子名称: Voltage-dependent L-type calcium channel subunit alpha-1C, Voltage-dependent calcium channel subunit alpha-2/delta-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: cav1.2, channels, calcium ion-selective, transport protein, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 375854.19

構造登録者

Gao, S.,Yao, X.,Fan, X.,Yan, N. (登録日: 2023-09-17, 公開日: 2023-12-06, 最終更新日: 2025-07-02)

主引用文献

Gao, S.,Yao, X.,Chen, J.,Huang, G.,Fan, X.,Xue, L.,Li, Z.,Wu, T.,Zheng, Y.,Huang, J.,Jin, X.,Wang, Y.,Wang, Z.,Yu, Y.,Liu, L.,Pan, X.,Song, C.,Yan, N.
Structural basis for human Ca v 1.2 inhibition by multiple drugs and the neurotoxin calciseptine.
Cell, 186:5363-5374.e16, 2023

PubMed Abstract: Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate.

PubMed: 37972591
DOI: 10.1016/j.cell.2023.10.007

実験手法

ELECTRON MICROSCOPY (3.2 Å)