Department of Chemistry, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
J Biol Chem. 2011 Apr 29;286(17):15496-506. doi: 10.1074/jbc.M110.189951. Epub 2011 Feb 23.
Host cell invasion by the facultative intracellular pathogen Listeria monocytogenes requires the invasion protein InlB in many cell types. InlB consists of an N-terminal internalin domain that binds the host cell receptor tyrosine kinase Met and C-terminal GW domains that bind to glycosaminoglycans (GAGs). Met binding and activation is required for host cell invasion, while the interaction between GW domains and GAGs enhances this effect. Soluble InlB elicits the same cellular phenotypes as the natural Met ligand hepatocyte growth factor/scatter factor (HGF/SF), e.g. cell scatter. So far, little is known about the central part of InlB, the B-repeat. Here we present a structural and functional characterization of the InlB B-repeat. The crystal structure reveals a variation of the β-grasp fold that is most similar to small ubiquitin-like modifiers (SUMOs). However, structural similarity also suggests a potential evolutionary relation to bacterial mucin-binding proteins. The B-repeat defines the prototype structure of a hitherto uncharacterized domain present in over a thousand bacterial proteins. Generally, this domain probably acts as a spacer or a receptor-binding domain in extracellular multi-domain proteins. In cellular assays the B-repeat acts synergistically with the internalin domain conferring to it the ability to stimulate cell motility. Thus, the B-repeat probably binds a further host cell receptor and thereby enhances signaling downstream of Met.
兼性细胞内病原体李斯特菌属单核细胞增生李斯特菌的宿主细胞入侵需要侵袭蛋白 InlB 在许多细胞类型中。InlB 由一个结合宿主细胞受体酪氨酸激酶 Met 的 N 端内部素结构域和一个结合糖胺聚糖（GAGs）的 C 端 GW 结构域组成。Met 结合和激活是宿主细胞入侵所必需的，而 GW 结构域与 GAGs 之间的相互作用增强了这种效应。可溶性 InlB 引发与天然 Met 配体肝细胞生长因子/分散因子 (HGF/SF) 相同的细胞表型，例如细胞分散。到目前为止，人们对 InlB 的中央部分 B-重复序列知之甚少。在这里，我们对 InlB B-重复序列进行了结构和功能表征。晶体结构揭示了β-抓握折叠的变化，与小泛素样修饰物 (SUMO) 最为相似。然而，结构相似性也暗示了与细菌粘蛋白结合蛋白的潜在进化关系。B-重复序列定义了一个迄今为止尚未表征的结构域的原型结构，该结构域存在于超过一千种细菌蛋白中。一般来说，这个结构域可能在细胞外多结构域蛋白中充当间隔子或受体结合结构域。在细胞测定中，B-重复序列与内部素结构域协同作用，赋予其刺激细胞运动的能力。因此，B-重复序列可能结合另一个宿主细胞受体，从而增强 Met 下游的信号转导。
