冷冻电镜结构揭示细菌外膜蛋白折叠的多个阶段
2022-03-20   阅读:465   来源:细胞

美国国立卫生研究院Harris D. Bernstein、Jenny E. Hinshaw等研究人员合作揭示细菌外膜蛋白折叠的多个阶段。该项研究成果于2022年3月15日在线发表在《细胞》杂志上。

研究人员表示,跨膜的β桶蛋白通过β桶装配机器(BAM)折叠到革兰氏阴性细菌的外膜(OM)中,这个过程不为人所知,而且发生时没有已知的外部能量来源。

通过使用单粒子冷冻电镜,研究人员观察了BAM对一个模型β桶蛋白(EspP)的折叠动态。结果发现,BAM与EspP高度保守的"β信号"模体结合,在折叠过程中正确引导OM中的β链。研究人员还发现,EspP的折叠是通过"杂交桶"中间物进行的,其中膜整合的β片被连接到重要的BAM亚单位BamA上。这些结构显示了EspP中间产物周围的膜出现了前所未有的偏转,并表明β片逐渐向BamA折叠,形成一个β桶。随着体内实验在改变OM张力的同时跟踪β桶的折叠,这些结果支持一个模型,即BAM利用OM的弹性来加速β桶的折叠。

附:英文原文

Title: Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding

Author: Matthew Thomas Doyle, John R. Jimah, Tyrone Dowdy, Shannon I. Ohlemacher, Mioara Larion, Jenny E. Hinshaw, Harris D. Bernstein

Issue&Volume: 2022-03-15

Abstract: Transmembrane β barrel proteins are folded into the outer membrane (OM) of Gram-negativebacteria by the β barrel assembly machinery (BAM) via a poorly understood processthat occurs without known external energy sources. Here, we used single-particle cryo-EMto visualize the folding dynamics of a model β barrel protein (EspP) by BAM. We foundthat BAM binds the highly conserved “β signal” motif of EspP to correctly orient βstrands in the OM during folding. We also found that the folding of EspP proceedsvia “hybrid-barrel” intermediates in which membrane integrated β sheets are attachedto the essential BAM subunit, BamA. The structures show an unprecedented deflectionof the membrane surrounding the EspP intermediates and suggest that β sheets progressivelyfold toward BamA to form a β barrel. Along with in vivo experiments that tracked β barrel folding while the OM tension was modified, ourresults support a model in which BAM harnesses OM elasticity to accelerate β barrelfolding.

DOI: 10.1016/j.cell.2022.02.016

编辑:小柯机器人

©2022年12月07日 07:54:03
基因在线
0.3214s加载完成
邮箱:info@jiyinzaixian.com