Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation.
Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation.
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DOI：
10.7554/elife.62614
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发表时间：
2020-12-14
期刊：
影响因子：
7.7
通讯作者：
Henderson IR
中科院分区：
文献类型：
--
作者：
Bryant JA;Morris FC;Knowles TJ;Maderbocus R;Heinz E;Boelter G;Alodaini D;Colyer A;Wotherspoon PJ;Staunton KA;Jeeves M;Browning DF;Sevastsyanovich YR;Wells TJ;Rossiter AE;Bavro VN;Sridhar P;Ward DG;Chong ZS;Goodall EC;Icke C;Teo AC;Chng SS;Roper DI;Lithgow T;Cunningham AF;Banzhaf M;Overduin M;Henderson IR
革兰氏阴性外膜包裹细菌，并作为抵抗抗生素、洗涤剂和环境压力的渗透性屏障。一些毒力因子用于维持外膜的完整性，包括DolP（以前的YraP），一种结构和功能尚未解决的蛋白质。在这里，我们揭示了DolP是革兰氏阴性菌中功能保守的脂蛋白，并且DolP的丧失增加了膜流动性。我们提出了大肠杆菌DolP，这是由两个BON域，形成一个相互连接的相对对的NMR溶液结构。C-末端BON结构域通过广泛的膜：蛋白质界面结合阴离子磷脂。这种相互作用对于DolP功能是必不可少的，并且是蛋白质在细胞分裂位点的亚细胞定位所必需的，提供了这些磷脂在外膜内的亚细胞定位的证据。DolP的结构为开发破坏细菌细胞包膜完整性的疗法提供了新的靶点。
The Gram-negative outer-membrane envelops the bacterium and functions as a permeability barrier against antibiotics, detergents, and environmental stresses. Some virulence factors serve to maintain the integrity of the outer membrane, including DolP (formerly YraP) a protein of unresolved structure and function. Here, we reveal DolP is a lipoprotein functionally conserved amongst Gram-negative bacteria and that loss of DolP increases membrane fluidity. We present the NMR solution structure for Escherichia coli DolP, which is composed of two BON domains that form an interconnected opposing pair. The C-terminal BON domain binds anionic phospholipids through an extensive membrane:protein interface. This interaction is essential for DolP function and is required for sub-cellular localisation of the protein to the cell division site, providing evidence of subcellular localisation of these phospholipids within the outer membrane. The structure of DolP provides a new target for developing therapies that disrupt the integrity of the bacterial cell envelope.