Peptidoglycan maturation controls outer membrane protein assembly.
Peptidoglycan maturation controls outer membrane protein assembly.
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DOI：
10.1038/s41586-022-04834-7
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发表时间：
2022-06
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
革兰氏阴性菌的外膜和肽聚糖层之间的连接对于维持细胞完整性至关重要，并使其能够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），它们通过β-桶组装机（BAM）插入膜中。生长中的大肠杆菌细胞通过一种称为二元分配的过程将旧的外膜蛋白向两极分离，这种过程的基础尚不清楚。在这里，我们表明，肽聚糖的时空组织的外膜蛋白的基础。成熟的富含四肽的肽聚糖与BAM组分结合并抑制OMP折叠酶活性。新生肽聚糖，这是丰富的五肽和集中在隔膜，与BAM差，并对其活性几乎没有影响，导致优先插入的OMPs在分裂网站。OMP生物发生与细胞壁生长的同步导致OMP在细胞分裂时的二元分配。我们的研究表明，革兰氏阴性菌协调组装两个主要的细胞包膜层，使OMP生物合成响应肽聚糖成熟，一个潜在的脆弱性，可以利用在未来的抗生素设计。革兰氏阴性细菌细胞壁中的肽聚糖干肽调节必需外膜蛋白的插入，因此代表抗生素设计的潜在靶标。
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 environments. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown. 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 septa, 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. Peptidoglycan stem peptides in the Gram-negative bacterial cell wall regulate the insertion of essential outer membrane proteins, thus representing a potential target for antibiotic design.
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影响因子：
7.7
作者：
Alvira S;Watkins DW;Troman L;Allen WJ;Lorriman JS;Degliesposti G;Cohen EJ;Beeby M;Daum B;Gold VA;Skehel JM;Collinson I
通讯作者：
Collinson I
DOI：
10.1126/science.aad3460
发表时间：
2016-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bakelar J;Buchanan SK;Noinaj N
通讯作者：
Noinaj N
影响因子：
6.4
作者：
Behrens, Hannah M.;Lowe, Edward D.;Kleanthous, Colin
通讯作者：
Kleanthous, Colin
影响因子：
64.5
作者：
Doyle MT;Jimah JR;Dowdy T;Ohlemacher SI;Larion M;Hinshaw JE;Bernstein HD
通讯作者：
Bernstein HD
影响因子：
16.6
作者：
Iadanza, Matthew G.;Higgins, Anna J.;Schiffrin, Bob;Calabrese, Antonio N.;Brockwell, David J.;Ashcroft, Alison E.;Radford, Sheena E.;Ranson, Neil A.
通讯作者：
Ranson, Neil A.