Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation.

Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation.
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DOI:
10.1111/j.1365-2958.2007.06054.x
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发表时间:
2008-01
影响因子:
3.6
通讯作者:
Matthews S
Matthews S
中科院分区:
生物学2区
文献类型:
--
作者:
Korotkova N;Yang Y;Le Trong I;Cota E;Demeler B;Marchant J;Thomas WE;Stenkamp RE;Moseley SL;Matthews S

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癌胚抗原(CEA)相关细胞粘附分子(CEACAMs)是大肠杆菌粘附素Dr家族的受体。为了确定Dr粘附素与CEACAM受体结合的机制,我们对CEA的N-末端结构域及其与Dr粘附素的复合物进行了结构研究。CEA的晶体结构揭示了类似于由具有IgV样结构域的受体形成的其他二聚体的二聚体。CEA/Dr粘附素复合物的结构是基于NMR光谱和诱变数据结合生化表征提出的。Dr粘附素/CEA界面与负责CEA二聚化的区域明显重叠。CEA二聚体的结合动力学、突变分析和光谱检查表明,Dr粘附素可以在单体形式结合之前解离CEA二聚体。我们的结论包括一个合理的机制,如何E。大肠杆菌,也许还有其他细菌和病毒病原体,利用CEACAMs。该复合物目前的结构为设计新的治疗大肠杆菌的抑制策略提供了有力的工具。大肠杆菌感染。
Carcinoembryonic antigen (CEA) related cell adhesion molecules (CEACAMs) are host receptors for the Dr family of adhesins of Escherichia coli. To define the mechanism for binding of Dr adhesins to CEACAM receptors, we carried out structural studies on the N-terminal domain of CEA and its complex with the Dr adhesin. The crystal structure of CEA reveals a dimer similar to other dimers formed by receptors with IgV-like domains. The structure of the CEA/Dr adhesin complex is proposed based on NMR spectroscopy and mutagenesis data in combination with biochemical characterization. The Dr adhesin/CEA interface overlaps appreciably with the region responsible for CEA dimerization. Binding kinetics, mutational analysis, and spectroscopic examination of CEA dimers suggest that Dr adhesins can dissociate CEA dimers prior to the binding of monomeric forms. Our conclusions include a plausible mechanism for how E. coli, and perhaps other bacterial and viral pathogens, exploit CEACAMs. The present structure of the complex provides a powerful tool for the design of novel inhibitory strategies to treat E. coli infections.
DOI: 10.1111/j.1365-2958.2004.04033.x
发表时间: 2004-05-01
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