Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin
Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin
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DOI：
10.1016/s0092-8674(02)01136-4
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发表时间：
2002-12-13
期刊：
影响因子：
64.5
通讯作者：
Heinz, DW
中科院分区：
文献类型：
--
作者：
Schubert, WD;Urbanke, C;Heinz, DW
单核细胞增生李斯特菌是一种食源性致病菌，通过诱导自身的吞噬作用进入哺乳动物细胞。肠道蛋白质内化素（InIA）通过与宿主细胞受体E-cadherin的特异性相互作用介导细菌粘附和侵袭人类肠道上皮细胞。我们提出的晶体结构的功能域的InIA单独和在一个复杂的细胞外，N-末端结构域的人E-钙粘蛋白（hEC 1）。InIA的富含亮氨酸的重复序列（LRR）结构域围绕并特异性识别hEC 1。通过诱变和分析性超离心来探测个体相互作用。这些包括hEC 1的Pro 16，这是人类对L易感性的主要决定因素。单核细胞增多症感染是分子间识别所必需的。我们的研究揭示了该菌寄主嗜性的结构基础和分子欺骗L。单核细胞增多症利用E-钙粘蛋白系统。
Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells by inducing its own phagocytosis. The listerial protein internalin (InIA) mediates bacterial adhesion and invasion of epithelial cells in the human intestine through specific interaction with its host cell receptor E-cadherin. We present the crystal structures of the functional domain of InIA alone and in a complex with the extracellular, N-terminal domain of human E-cadherin (hEC1). The leucine rich repeat (LRR) domain of InIA surrounds and specifically recognizes hEC1. Individual interactions were probed by mutagenesis and analytical ultracentrifugation. These include Pro16 of hEC1, a major determinant for human susceptibility to L. monocytogenes infection that is essential for intermolecular recognition. Our studies reveal the structural basis for host tropism of this bacterium and the molecular deception L. monocytogenes employs to exploit the E-cadherin system.