Department of Pharmacology, Columbia University, NY, USA.
Department of Ophthalmology, Columbia University, NY, USA.
Channels (Austin). 2021 Dec;15(1):604-623. doi: 10.1080/19336950.2021.1981625.
Bestrophins are a family of calcium-activated chloride channels (CaCCs) with relevance to human physiology and a myriad of eye diseases termed "bestrophinopathies". Since the identification of bestrophins as CaCCs nearly two decades ago, extensive studies from electrophysiological and structural biology perspectives have sought to define their key channel features including calcium sensing, gating, inactivation, and anion selectivity. The initial X-ray crystallography studies on the prokaryotic homolog of Best1, (KpBest), and the Best1 homolog from (chicken Best1, cBest1), laid the foundational groundwork for establishing the architecture of Best1. Recent progress utilizing single-particle cryogenic electron microscopy has further elucidated the molecular mechanism of gating in cBest1 and, separately, the structure of Best2 from (bovine Best2, bBest2). Meanwhile, whole-cell patch clamp, planar lipid bilayer, and other electrophysiologic analyses using these models as well as the human Best1 (hBest1) have provided ample evidence describing the functional properties of the bestrophin channels. This review seeks to consolidate these structural and functional results to paint a broad picture of the underlying mechanisms comprising the bestrophin family's structure-function relationship.
Bestrophins 是一组钙激活氯离子通道 (CaCCs)，与人类生理学和多种眼病（称为“Bestrophinopathies”）有关。自近二十年前鉴定出 Bestrophins 为 CaCCs 以来，从电生理学和结构生物学的角度进行了广泛的研究，旨在定义其关键通道特性，包括钙感应、门控、失活和阴离子选择性。最初对 Best1 的原核同源物 （KpBest） 和来自 （鸡 Best1，cBest1）的 Best1 同源物的 X 射线晶体学研究为确定 Best1 的结构奠定了基础。最近利用单颗粒低温电子显微镜的进展进一步阐明了 cBest1 中门控的分子机制，以及分别来自 （牛 Best2，bBest2）的 Best2 的结构。同时，使用这些模型的全细胞膜片钳、平面脂质双层和其他电生理分析以及人 Best1（hBest1）提供了大量证据，描述了 Bestrophin 通道的功能特性。本综述旨在整合这些结构和功能结果，以描绘组成 Bestrophin 家族结构-功能关系的基本机制的全貌。
