小柯机器人

新生膜蛋白在BAM复合物上折叠时的结构
2020-06-12 22:04

美国哈佛大学医学院Daniel Kahne、Zongli Li和Stephen C. Harrison研究组合作取得新进展。他们解析了新生膜蛋白在β桶装配机器(BAM)复合物上折叠时的结构。2020年6月11日,《自然》杂志发表了这一成果。

他们报告了折叠BamA大肠杆菌BAM复合物的结构。BamA催化剂与BamA底物形成不对称杂化β-桶。BamA催化剂的N端边缘与BamA底物的C端边缘具有反平行的氢键界面,与以前的交联研究一致。BamA催化剂和底物的其他边缘彼此靠近,但向内卷曲且不成对。

膜环境中的六个氢键使两种蛋白质之间的界面非常稳定。这种稳定性允许折叠,但是在折叠完成后对底物的释放产生了很高的动力学屏障。底物两端的特征克服了这一障碍,并通过逐步交换氢键促进释放。底物辅助产物释放的这种机制解释了BAM复合物如何在折叠过程中稳定地与底物结合,然后在折叠完成后迅速翻转。

据介绍,线粒体、叶绿体和革兰氏阴性细菌被包裹在双层膜中。外膜含有具有β-桶状结构的蛋白质。β-桶是包裹在圆柱体中的β链片,其中第一链氢键连结到最终链。保守的多亚基分子机器折叠并将这些蛋白质插入外膜。机器的一个亚基本身就是β-桶蛋白,它在折叠其他β-桶时起着核心作用。在革兰氏阴性细菌中,BAM由β桶蛋白BamA和四个脂蛋白组成。为了了解BAM复合物如何在不使用外来能量(例如ATP)的情况下,加快折叠速度,他们将折叠中间体捕获在该机器上。

附:英文原文

Title: Structure of a nascent membrane protein as it folds on the BAM complex

Author: David Tomasek, Shaun Rawson, James Lee, Joseph S. Wzorek, Stephen C. Harrison, Zongli Li, Daniel Kahne

Issue&Volume: 2020-06-11

Abstract: Mitochondria, chloroplasts and Gram-negative bacteria are encased in a double layer of membranes. The outer membrane contains proteins with a β-barrel structure1,2. β-Barrels are sheets of β-strands wrapped into a cylinder, in which the first strand is hydrogen-bonded to the final strand. Conserved multi-subunit molecular machines fold and insert these proteins into the outer membrane3,4,5. One subunit of the machines is itself a β-barrel protein that has a central role in folding other β-barrels. In Gram-negative bacteria, the β-barrel assembly machine (BAM) consists of the β-barrel protein BamA, and four lipoproteins5,6,7,8. To understand how the BAM complex accelerates folding without using exogenous energy (for example, ATP)9, we trapped folding intermediates on this machine. Here we report the structure of the BAM complex of Escherichia coli folding BamA itself. The BamA catalyst forms an asymmetric hybrid β-barrel with the BamA substrate. The N-terminal edge of the BamA catalyst has an antiparallel hydrogen-bonded interface with the C-terminal edge of the BamA substrate, consistent with previous crosslinking studies10,11,12; the other edges of the BamA catalyst and substrate are close to each other, but curl inward and do not pair. Six hydrogen bonds in a membrane environment make the interface between the two proteins very stable. This stability allows folding, but creates a high kinetic barrier to substrate release after folding has finished. Features at each end of the substrate overcome this barrier and promote release by stepwise exchange of hydrogen bonds. This mechanism of substrate-assisted product release explains how the BAM complex can stably associate with the substrate during folding and then turn over rapidly when folding is complete.

DOI: 10.1038/s41586-020-2370-1

Source: https://www.nature.com/articles/s41586-020-2370-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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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