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清华肖百龙/李雪明合作解析机械门控通道PIEZO2
2019-08-22 13:00

清华大学肖百龙、李雪明研究组合作解析了机械门控通道PIEZO2结构。这一研究成果发表于2019年8月22日在线发表在国际学术期刊《自然》上。

研究人员描述了小鼠PIEZO2的冷冻电镜结构,它是一个三叶片螺旋桨状的三聚体,包含114个跨膜螺旋(每个原聚体38个)。跨膜螺旋1-36(TM1-36)被折叠成九个串联单元,每个具有四个跨膜螺旋,从而形成不同寻常的非平面叶片。三个叶片共同弯曲成直径28nm、深度10nm的纳米圆顶,并带有中心嵌入细胞外帽状结构以及连接中心孔的9nm细胞内束。TM38和C-末端结构域被锚定结构域和TM37所环绕,并且中心孔由跨膜的和细胞质的收缩位点所包围。PIEZO2与其同源物PIEZO1之间的结构比较表明,跨膜收缩位点可能充当由帽结构域控制的跨膜门。总之,这项研究提供了对压电通道的结构和机械化机制的见解。

研究人员表示,PIEZO2是一种机械敏感阳离子通道,在感知触觉、触觉疼痛、呼吸和血压方面起着关键作用。

附:英文原文

Title: Structure and mechanogating of the mammalian tactile channel PIEZO2

Author: Li Wang, Heng Zhou, Mingmin Zhang, Wenhao Liu, Tuan Deng, Qiancheng Zhao, Yiran Li, Jianlin Lei, Xueming Li, Bailong Xiao

Issue&Volume: 2019-08-21

Abstract: PIEZO2 is a mechanosensitive cation channel that has a key role in sensing touch, tactile pain, breathing and blood pressure. Here we describe the cryo-electron microscopy structure of mouse PIEZO2, which is a three-bladed, propeller-like trimer that comprises 114 transmembrane helices (38 per protomer). Transmembrane helices 136 (TM136) are folded into nine tandem units of four transmembrane helices each to form the unusual non-planar blades. The three blades are collectively curved into a nano-dome of 28-nm diameter and 10-nm depth, with an extracellular cap-like structure embedded in the centre and a 9-nm-long intracellular beam connecting to the central pore. TM38 and the C-terminal domain are surrounded by the anchor domain and TM37, and enclose the central pore with both transmembrane and cytoplasmic constriction sites. Structural comparison between PIEZO2 and its homologue PIEZO1 reveals that the transmembrane constriction site might act as a transmembrane gate that is controlled by the cap domain. Together, our studies provide insights into the structure and mechanogating mechanism of Piezo channels.

DOI: 10.1038/s41586-019-1505-8

Source:https://www.nature.com/articles/s41586-019-1505-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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