期刊
BIOPHYSICAL JOURNAL
卷 122, 期 3, 页码 496-505出版社
CELL PRESS
DOI: 10.1016/j.bpj.2022.12.037
关键词
-
类别
Cav1.1 is a voltage-gated calcium channel essential for skeletal muscle contraction. Molecular dynamics simulations revealed the existence of two Ca2+-binding sites, S1 and S2, within the selectivity filter of Cav1.1. These findings enhance our understanding of ion permeation and selectivity in calcium channels.
Cav1.1 is the voltage-gated calcium channel essential for the contraction of skeletal muscles upon membrane potential changes. Structural determination of the Cav1.1 channel opens the avenue toward understanding of the structure-func-tion relationship of voltage-gated calcium channels. Here, we show that there exist two Ca2+-binding sites, termed S1 and S2, within the selectivity filter of Cav1.1 through extensive molecular dynamics simulations on various initial ion arrangement configurations. The formation of both binding sites is associated with the four Glu residues (Glu292/614/1014/1323) that consti-tute the so-called EEEE locus. At the S1 site near the extracellular side, the Ca2+ ion is coordinated with the negatively charged carboxylic groups of these Glu residues and of the Asp615 residue either in a direct way or via an intermediate water molecule. At the S2 site, Ca2+ binding shows two distinct states: an upper state involving two out of the four Glu residues in the EEEE locus and a lower state involving only one Glu residue. In addition, there exist two recruitment sites for Ca2+ above the entrance of the filter. These findings promote the understanding of mechanism for ion permeation and selectivity in calcium channels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据