Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
FEBS Lett. 2014 Apr 17;588(8):1230-7. doi: 10.1016/j.febslet.2014.01.042. Epub 2014 Feb 1.
Connexin gap junctions comprise assembled channels penetrating two plasma membranes for which gating regulation is associated with a variety of factors, including voltage, pH, Ca(2+), and phosphorylation. Functional studies have established that various parts of the connexin peptides are related to channel closure and electrophysiology studies have provided several working models for channel gating. The corresponding structural models supporting these findings, however, are not sufficient because only small numbers of closed connexin structures have been reported. To fully understand the gating mechanisms, the channels should be visualized in both the open and closed states. Electron crystallography and X-ray crystallography studies recently revealed three-dimensional structures of connexin channels in a couple of states in which the main difference is the conformation of the N-terminal domain, which have helped to clarify the structure in regard to channel closure. Here the closure models for connexin gap junction channels inferred from structural and functional studies are described in the context of each domain of the connexin protein associated with gating modulation.
缝隙连接由组装好的通道穿透两个质膜构成，其门控调节与多种因素相关，包括电压、pH 值、Ca(2+)和磷酸化。功能研究已经证实，连接子肽的各个部分与通道关闭有关，电生理学研究已经为通道门控提供了几个工作模型。然而，支持这些发现的相应结构模型还不够充分，因为只有少数封闭的连接子结构被报道。为了充分理解门控机制，应该在开放和关闭状态下可视化通道。电子晶体学和 X 射线晶体学研究最近揭示了几个状态下连接子通道的三维结构，其主要区别在于 N 端结构域的构象，这有助于阐明与通道关闭相关的结构。本文将描述从结构和功能研究中推断出的连接子缝隙连接通道的关闭模型，其涉及与门控调节相关的连接子蛋白的各个结构域。
