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肽聚糖成熟控制外膜蛋白的组装
2022-06-19 11:47

英国纽卡斯尔大学Waldemar Vollmer、剑桥大学Colin Kleanthous等研究人员合作发现,肽聚糖成熟控制外膜蛋白的组装。相关论文于2022年6月15日在线发表在《自然》杂志上。

据研究人员介绍,革兰氏阴性菌的外膜和肽聚糖层之间的联系对维持细胞的完整性至关重要,并能在具有挑战性的环境中生存。外膜的功能依赖于外膜蛋白(OMP),它们由β-桶状装配机器(BAM)插入膜中。生长中的大肠杆菌细胞通过一个被称为二元分割的过程将旧的OMP向两极分离,其基础尚不清楚。
 
研究人员证明肽聚糖是OMP时空组织的基础。成熟的、富含四肽的肽聚糖与BAM组件结合,抑制OMP折叠酶的活性。富含五肽的新生肽聚糖,集中在隔膜,与BAM结合得很差,对其活性影响不大,导致OMP优先插入分裂点。OMP生物生成与细胞壁生长的同步性导致细胞分裂时OMP的二元分割。这项研究揭示,革兰氏阴性菌通过使OMP生物生成对肽聚糖的成熟作出反应来协调两个主要细胞包膜层的组装,这是一个潜在的漏洞,可以在未来的抗生素设计中加以利用。
 
附:英文原文

Title: Peptidoglycan maturation controls outer membrane protein assembly

Author: Mamou, Gideon, Corona, Federico, Cohen-Khait, Ruth, Housden, Nicholas G., Yeung, Vivian, Sun, Dawei, Sridhar, Pooja, Pazos, Manuel, Knowles, Timothy J., Kleanthous, Colin, Vollmer, Waldemar

Issue&Volume: 2022-06-15

Abstract: Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments1,2,3,4,5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine6,7 (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown8. Here we demonstrate that peptidoglycan underpins the spatiotemporal organization of OMPs. Mature, tetrapeptide-rich peptidoglycan binds to BAM components and suppresses OMP foldase activity. Nascent peptidoglycan, which is enriched in pentapeptides and concentrated at septa9, associates with BAM poorly and has little effect on its activity, leading to preferential insertion of OMPs at division sites. The synchronization of OMP biogenesis with cell wall growth results in the binary partitioning of OMPs as cells divide. Our study reveals that Gram-negative bacteria coordinate the assembly of two major cell envelope layers by rendering OMP biogenesis responsive to peptidoglycan maturation, a potential vulnerability that could be exploited in future antibiotic design.

DOI: 10.1038/s41586-022-04834-7

Source: https://www.nature.com/articles/s41586-022-04834-7

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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