Structure and Function of the Bestrophin family of calcium-activated chloride channels.

Structure and Function of the Bestrophin family of calcium-activated chloride channels.
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DOI:
10.1080/19336950.2021.1981625
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发表时间:
2021-12
期刊:
Channels (Austin, Tex.)
影响因子:
--
通讯作者:
Yang T
Yang T
中科院分区:
其他
文献类型:
--
作者:
Owji AP;Kittredge A;Zhang Y;Yang T

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Bestrophins是一个钙活化的氯离子通道(CaCCs)家族,与人体生理学和无数被称为“bestrophinopathies”的眼病有关。自从近20年前确定嗜中性粒细胞为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,试图定义它们的关键通道特征,包括钙感知、门控、失活和阴离子选择性。通过对Best1与肺炎克雷伯菌(Klebsiella pneumoniae, KpBest)和鸡(Gallus Gallus) Best1同源物(chicken Best1, cBest1)的x射线晶体学初步研究,为建立Best1的结构奠定了基础。近年来利用单粒子低温电子显微镜的研究进展进一步阐明了bbest - 1中的门控分子机制,以及牛牛的bBest2 (bovine Best2, bBest2)的结构。同时,全细胞膜片钳、平面脂质双分子层和其他电生理分析使用这些模型以及人类Best1 (hBest1)提供了充分的证据来描述strophin通道的功能特性。本综述旨在巩固这些结构和功能的结果,以描绘一个广泛的潜在机制,包括strophin家族的结构-功能关系。
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, Klebsiella pneumoniae (KpBest), and the Best1 homolog from Gallus gallus (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 Bos taurus (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.
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