PDF(Pubmed)
Abstract：
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.
摘要：
近年来，环核苷酸门控（CNG）通道的原子或近原子分辨率结构大量涌现，在封闭中被捕获，过渡,预开放,部分开放,完全开放的国家。这些结构为激活提供了前所未有的分子见解，装配,architecture,regulation,和CNG通道的通道作用，以及CNG通道生物物理和药理特性的机械解释。本文总结了CNG通道结构生物学的最新进展，描述了关键的结构特征和元素，并阐明了环核苷酸激活的详细构象景观。该综述还将结构与功能研究中描述的发现和属性相关联，包括非选择性单价阳离子选择性，Ca2+渗透和阻塞，用L-顺式地尔硫卓阻滞，激活门的位置，缺乏依赖电压的门控，和脂质和钙调蛋白的调节。并对未来的研究提出了展望。
