Structure of the bacterial cell division determinant GpsB and its interaction with penicillin‐binding proteins

Structure of the bacterial cell division determinant GpsB and its interaction with penicillin‐binding proteins
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细菌细胞分裂决定子GpsB的结构及其与青霉素结合蛋白的相互作用

DOI:
10.1111/mmi.13279
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发表时间:
2016
影响因子:
3.6
通讯作者:
Halbedel
Halbedel
中科院分区:
生物学2区
文献类型:
--
作者:
Rismondo;Cleverley;Großhennig;Steglich;Möller;Mannala;Halbedel

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每个细菌都必须协调其生长与分裂,以确保种群的遗传稳定性。因此,细胞分裂和生长是受到严格调控的现象,尽管不同的细菌利用几种替代调控机制之一来维持控制。在这里,我们考虑GpsB,它与革兰氏阳性细菌的细胞生长和分裂有关。单核细胞增生李斯特菌(Listeria monocytogenes)Δ gpsB突变体由于细胞壁生物合成的扭曲而表现出严重的裂解、分裂和生长缺陷。与此前提一致,GpsB在体外和体内都与主要的双功能青霉素结合蛋白相互作用。我们解决了GpsB的晶体结构和相互作用的界面在两种蛋白质的识别和验证。在动物实验中,gpsB的失活导致毒力的强烈减弱,其程度与经典的细菌毒力因子突变体相当。因此,GpsB对于高毒性食源性病原体的体外和体内生长至关重要,这表明GpsB可能是未来新型抗菌药物设计的目标。
Each bacterium has to co‐ordinate its growth with division to ensure genetic stability of the population. Consequently, cell division and growth are tightly regulated phenomena, albeit different bacteria utilise one of several alternative regulatory mechanisms to maintain control. Here we consider GpsB, which is linked to cell growth and division in Gram‐positive bacteria. ΔgpsBmutants of the human pathogenListeria monocytogenesshow severe lysis, division and growth defects due to distortions of cell wall biosynthesis. Consistent with this premise, GpsB interacts bothin vitroandin vivowith the major bi‐functional penicillin‐binding protein. We solved the crystal structure of GpsB and the interaction interfaces in both proteins are identified and validated. The inactivation ofgpsBresults in strongly attenuated virulence in animal experiments, comparable in degree to classical listerial virulence factor mutants. Therefore, GpsB is essential forin vitroandin vivogrowth of a highly virulent food‐borne pathogen, suggesting that GpsB could be a target for the future design of novel antibacterials.
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