SipC multimerization promotes actin nucleation and contributes to Salmonella-induced inflammation
SipC multimerization promotes actin nucleation and contributes to Salmonella-induced inflammation
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DOI：
10.1111/j.1365-2958.2007.06024.x
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Zhou, Daoguo
中科院分区：
文献类型：
--
作者：
Chang, JiHoon;Myeni, Sebenzile K.;Zhou, Daoguo
肌动蛋白成核是肌动蛋白组装的限速步骤，受肌动蛋白结合蛋白和信号转导分子的调控。鼠伤寒沙门氏菌通过重组宿主肌动蛋白细胞骨架以促进自身的摄取，从而利用肌动蛋白动力学。SipC是一种沙门氏菌肌动蛋白结合蛋白，在体外可促使肌动蛋白丝形成核。SipC促使肌动蛋白成核的分子机制尚不清楚。在此我们表明SipC(199 - 409)形成多聚体以促进肌动蛋白成核。我们发现野生型SipC(199 - 409)形成二聚体和多聚体，而一种成核突变体SipC(199 - 409)#1在二聚体和多聚体形成方面效率较低。生化分析表明SipC(199 - 409)可能以一种伸展的构象形成平行二聚体。此外，一种在形成SipC多聚体方面有缺陷且肌动蛋白成核不足的沙门氏菌突变株在小鼠模型中未能引发严重的结肠炎。这些结果使我们能够提出一个模型，即SipC形成多聚体以促进肌动蛋白成核。
Actin nucleation is the rate-limiting step in actin assembly and is regulated by actin-binding proteins and signal transduction molecules. Salmonella enterica serovar Typhimurium exploits actin dynamics by reorganizing the host actin cytoskeleton to facilitate its own uptake. SipC is a Salmonella actin-binding protein that nucleates actin filament formation in vitro. The molecular mechanism by which SipC nucleates actin is not known. We show here that SipC(199-409) forms multimers to promote actin nucleation. We found that wild-type SipC(199-409) forms dimers and multimers while SipC(199-409)#1, a nucleation mutant, is less efficient in dimer and multimer formation. Biochemical analysis suggested that SipC(199-409) might form parallel dimers in an extended conformation. Furthermore, a mutant Salmonella strain that was defective in forming the SipC multimer and deficient in actin nucleation failed to cause severe colitis in a mouse model. These results allow us to present a model in which SipC forms multimers to promote actin nucleation.