Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels.

Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels.
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环核苷酸门控通道的特性、机制和通道病变的结构基础。

DOI:
10.1080/19336950.2023.2273165
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发表时间:
2023-12
期刊:
影响因子:
3.3
通讯作者:
Yang, Jian
Yang, Jian
中科院分区:
生物学3区
文献类型:
--
作者:
Hu, Zhengshan;Yang, Jian

文献摘要

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近年来,环核苷酸门控(CNG)通道的原子或近原子分辨结构涌现出来,这些结构在关闭、过渡、预开放、部分开放和完全开放状态下捕获。这些结构为CNG通道的激活、组装、结构、调节和通道病变提供了前所未有的分子见解,也为CNG通道的生物物理和药理学特性提供了机制解释。本文综述了CNG通道结构生物学的最新进展,描述了CNG通道的关键结构特征和元件,阐明了环核苷酸激活CNG通道的详细构象图景。该综述还将结构与功能研究中描述的结果和性质联系起来,包括非选择性单价阳离子选择性、钙离子渗透和阻断、L-顺式地尔硫卓的阻断、激活门的位置、缺乏电压依赖的门控以及脂类和钙调蛋白的调节。并对未来的研究进行了展望。
Recent years have seen an outpouring of atomic or near atomic resolution structures of cyclic nucleotide-gated (CNG) channels, captured in closed, transition, pre-open, partially open, and fully open states. These structures provide unprecedented molecular insights into the activation, assembly, architecture, regulation, and channelopathy of CNG channels, as well as mechanistic explanations for CNG channel biophysical and pharmacological properties. This article summarizes recent advances in CNG channel structural biology, describes key structural features and elements, and illuminates a detailed conformational landscape of activation by cyclic nucleotides. The review also correlates structures with findings and properties delineated in functional studies, including nonselective monovalent cation selectivity, Ca2+ permeation and block, block by L-cis-diltiazem, location of the activation gate, lack of voltage-dependent gating, and modulation by lipids and calmodulin. A perspective on future research is also offered.
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