Ireton Keith, Rigano Luciano A, Polle Lilia, Schubert Wolf-Dieter
Department of Microbiology and Immunology, University of Otago Dunedin, New Zealand.
Department of Biotechnology, University of the Western Cape Bellville, Cape Town, South Africa.
Front Cell Infect Microbiol. 2014 Feb 21;4:21. doi: 10.3389/fcimb.2014.00021. eCollection 2014.
The bacterial pathogen Listeria monocytogenes spreads within human tissues using a motility process dependent on the host actin cytoskeleton. Cell-to-cell spread involves the ability of motile bacteria to remodel the host plasma membrane into protrusions, which are internalized by neighboring cells. Recent results indicate that formation of Listeria protrusions in polarized human cells involves bacterial antagonism of a host signaling pathway comprised of the scaffolding protein Tuba and its effectors N-WASP and Cdc42. These three human proteins form a complex that generates tension at apical cell junctions. Listeria relieves this tension and facilitates protrusion formation by secreting a protein called InlC. InlC interacts with a Src Homology 3 (SH3) domain in Tuba, thereby displacing N-WASP from this domain. Interaction of InlC with Tuba is needed for efficient Listeria spread in cultured human cells and infected animals. Recent structural data has elucidated the mechanistic details of InlC/Tuba interaction, revealing that InlC and N-WASP compete for partly overlapping binding surfaces in the Tuba SH3 domain. InlC binds this domain with higher affinity than N-WASP, explaining how InlC is able to disrupt Tuba/N-WASP complexes.
细菌病原体单核细胞增生李斯特菌利用依赖于宿主肌动蛋白细胞骨架的运动过程在人体组织内传播。细胞间传播涉及运动性细菌将宿主质膜重塑为突起的能力，这些突起会被邻近细胞内化。最近的研究结果表明，在极化的人体细胞中形成李斯特菌突起涉及对由支架蛋白Tuba及其效应蛋白N-WASP和Cdc42组成的宿主信号通路的细菌拮抗作用。这三种人类蛋白质形成一个复合物，在顶端细胞连接处产生张力。李斯特菌通过分泌一种名为InlC的蛋白质来缓解这种张力并促进突起形成。InlC与Tuba中的Src同源3（SH3）结构域相互作用，从而将N-WASP从该结构域中置换出来。InlC与Tuba的相互作用是李斯特菌在培养的人体细胞和受感染动物中有效传播所必需的。最近的结构数据阐明了InlC/Tuba相互作用的机制细节，揭示了InlC和N-WASP在Tuba SH3结构域中竞争部分重叠的结合表面。InlC比N-WASP以更高的亲和力结合该结构域，这解释了InlC如何能够破坏Tuba/N-WASP复合物。
