Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex.
Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex.
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DOI：
10.1038/s41467-017-00783-2
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发表时间：
2017-10-03
影响因子：
16.6
通讯作者：
Dessen A
中科院分区：
文献类型：
--
作者：
Contreras-Martel C;Martins A;Ecobichon C;Trindade DM;Matteï PJ;Hicham S;Hardouin P;Ghachi ME;Boneca IG;Dessen A
细菌细胞壁的生物合成是一个重要的过程，它需要多肽聚糖生物合成酶在参与细胞分裂（“分裂体”）和侧壁生长（“长体”）的多蛋白复合物中的协调活动。MreC是一种结构蛋白，在壁延伸过程中充当平台，支撑其他必要的肽聚糖生物合成大分子，如青霉素结合蛋白。尽管这些多部分综合体很重要，但由于它们相互作用的短暂性，它们的建筑细节仍然难以捉摸。在这里，我们展示了来自幽门螺杆菌的可溶性PBP2:MreC核心长体复合物和未络合的PBP2的晶体结构。PBP2在打开其n端区域时识别双翼MreC分子，露出作为结合平台的疏水拉链。PBP2:MreC界面对于体外蛋白质识别和维持细菌形状和生长都是必不可少的。这项工作可以可视化肽聚糖机械蛋白是如何支架的，揭示了可以通过定制抑制剂靶向的相互作用区域。细菌壁生物合成是一个复杂的过程，需要多种酶的协同作用。在这里，作者从结构上表征了参与肽聚糖延伸和交联的PBP2:MreC复合物，并证明其破坏导致幽门螺杆菌形状的丧失和无法维持生长。
Bacterial cell wall biosynthesis is an essential process that requires the coordinated activity of peptidoglycan biosynthesis enzymes within multi-protein complexes involved in cell division (the “divisome”) and lateral wall growth (the “elongasome”). MreC is a structural protein that serves as a platform during wall elongation, scaffolding other essential peptidoglycan biosynthesis macromolecules, such as penicillin-binding proteins. Despite the importance of these multi-partite complexes, details of their architecture have remained elusive due to the transitory nature of their interactions. Here, we present the crystal structures of the soluble PBP2:MreC core elongasome complex from Helicobacter pylori, and of uncomplexed PBP2. PBP2 recognizes the two-winged MreC molecule upon opening of its N-terminal region, revealing a hydrophobic zipper that serves as binding platform. The PBP2:MreC interface is essential both for protein recognition in vitro and maintenance of bacterial shape and growth. This work allows visualization as to how peptidoglycan machinery proteins are scaffolded, revealing interaction regions that could be targeted by tailored inhibitors. Bacterial wall biosynthesis is a complex process that requires the coordination of multiple enzymes. Here, the authors structurally characterize the PBP2:MreC complex involved in peptidoglycan elongation and cross-linking, and demonstrate that its disruption leads to loss of H. pylori shape and inability to sustain growth.
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影响因子：
3.6
作者：
Divakaruni, Arun V.;Baida, Cyril;Gober, James W.
通讯作者：
Gober, James W.
影响因子：
2.5
作者：
Gabadinho J;Beteva A;Guijarro M;Rey-Bakaikoa V;Spruce D;Bowler MW;Brockhauser S;Flot D;Gordon EJ;Hall DR;Lavault B;McCarthy AA;McCarthy J;Mitchell E;Monaco S;Mueller-Dieckmann C;Nurizzo D;Ravelli RB;Thibault X;Walsh MA;Leonard GA;McSweeney SM
通讯作者：
McSweeney SM
DOI：
10.1073/pnas.0507708102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Dye, NA;Pincus, Z;Gitai, Z
通讯作者：
Gitai, Z
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.6
作者：
El Ghachi, Meriem;Matteie, Pierre-Jean;Boneca, Ivo G.
通讯作者：
Boneca, Ivo G.