Molecular mimicry enables competitive recruitment by a natively disordered protein
Molecular mimicry enables competitive recruitment by a natively disordered protein
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DOI：
10.1021/ja070153n
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发表时间：
2007-04-18
影响因子：
15
通讯作者：
Kleanthous, Colin
中科院分区：
文献类型：
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作者：
Bonsor, Daniel A.;Grishkovskaya, Irina;Kleanthous, Colin
我们报道了大肠杆菌 TolB-Pal 复合物的晶体结构，这是一种蛋白质-蛋白质复合物，参与维持所有革兰氏阴性细菌外膜 (OM) 的完整性，这些细菌被大肠菌素（蛋白质抗生素）寄生，以加快其进入细胞的速度。核酸酶大肠菌素利用其天然无序区域 (NDR) 竞争性招募 TolB，以破坏其与 Pal 的复合物，这被认为会触发毒素在局部不稳定的 OM 中易位。该结构显示肽聚糖相关脂蛋白 (Pal) 与 TolB 的 β 螺旋桨结构域的诱导拟合结合，导致其 α 螺旋之一的 N 末端解旋，并且几个残基发生构象的实质性变化。已知由此产生的与 TolB 的相互作用对于复合物和细菌 OM 的稳定性至关重要。与 TolB-大肠菌素 NDR 复合物的结构比较表明，大肠菌素在 Pal 位点结合，模仿重排的 Pal 残基，同时似乎阻止 TolB 中的诱导拟合变化。因此，这项研究解释了大肠杆菌素如何在细菌周质中招募 TolB，并强调了一种天然无序蛋白质的新结合机制。
We report the crystal structure of the Escherichia coli TolB-Pal complex, a protein-protein complex involved in maintaining the integrity of the outer membrane (OM) in all Gram-negative bacteria that is parasitized by colicins (protein antibiotics) to expedite their entry into cells. Nuclease colicins competitively recruit TolB using their natively disordered regions (NDRs) to disrupt its complex with Pal, which is thought to trigger translocation of the toxin across a locally destabilized OM. The structure shows induced-fit binding of peptidoglycan-associated lipoprotein (Pal) to the beta-propeller domain of TolB causing the N-terminus of one of its alpha-helices to unwind and several residues to undergo substantial changes in conformation. The resulting interactions with TolB are known to be essential for the stability of the complex and the bacterial OM. Structural comparisons with a TolB-colicin NDR complex reveal that colicins bind at the Pal site, mimicking rearranged Pal residues while simultaneously appearing to block induced-fit changes in TolB. The study therefore explains how colicins recruit TolB in the bacterial periplasm and highlights a novel binding mechanism for a natively disordered protein.