Niemann Hartmut H, Jäger Volker, Butler P Jonathan G, van den Heuvel Joop, Schmidt Sabine, Ferraris Davide, Gherardi Ermanno, Heinz Dirk W
Division of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Cell. 2007 Jul 27;130(2):235-46. doi: 10.1016/j.cell.2007.05.037.
The tyrosine kinase Met, the product of the c-met proto-oncogene and the receptor for hepatocyte growth factor/scatter factor (HGF/SF), mediates signals critical for cell survival and migration. The human pathogen Listeria monocytogenes exploits Met signaling for invasion of host cells via its surface protein InlB. We present the crystal structure of the complex between a large fragment of the human Met ectodomain and the Met-binding domain of InlB. The concave face of the InlB leucine-rich repeat region interacts tightly with the first immunoglobulin-like domain of the Met stalk, a domain which does not bind HGF/SF. A second contact between InlB and the Met Sema domain locks the otherwise flexible receptor in a rigid, signaling competent conformation. Full Met activation requires the additional C-terminal domains of InlB which induce heparin-mediated receptor clustering and potent signaling. Thus, although it elicits a similar cellular response, InlB is not a structural mimic of HGF/SF.
酪氨酸激酶Met是原癌基因c-met的产物，也是肝细胞生长因子/分散因子（HGF/SF）的受体，介导对细胞存活和迁移至关重要的信号。人类病原体单核细胞增生李斯特菌通过其表面蛋白InlB利用Met信号传导侵入宿主细胞。我们展示了人类Met胞外域的一个大片段与InlB的Met结合域之间复合物的晶体结构。InlB富含亮氨酸重复区域的凹面与Met柄的第一个免疫球蛋白样结构域紧密相互作用，该结构域不结合HGF/SF。InlB与Met信号素结构域之间的第二次接触将原本灵活的受体锁定在刚性的、有信号传导能力的构象中。完整的Met激活需要InlB额外的C末端结构域，其诱导肝素介导的受体聚集和强效信号传导。因此，尽管InlB引发类似的细胞反应，但它不是HGF/SF的结构模拟物。
