Characterization of a Listeria monocytogenes protein interfering with Rab5a
Characterization of a Listeria monocytogenes protein interfering with Rab5a
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DOI：
10.1111/j.1600-0854.2007.00683.x
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发表时间：
2008-03-01
期刊：
影响因子：
4.5
通讯作者：
Carrasco-Marin, Eugenio
中科院分区：
文献类型：
--
作者：
Alvarez-Dominguez, Carmen;Madrazo-Toca, Fidel;Carrasco-Marin, Eugenio
单核细胞增生李斯特菌（LM）的吞噬策略意味着招募和抑制Rab 5a。在这里，我们确定了李斯特菌蛋白结合Rab 5a，并负责Rab 5a招聘吞噬体和GDP/GTP交换活性的损害。该蛋白被鉴定为来自李斯特菌的甘油醛-3-磷酸脱氢酶（GAPDH）（p40蛋白，Lmo 2459）。p40蛋白存在于吞噬体膜内。LM p40蛋白的序列分析揭示了两个酶结构域：N端的烟酰胺腺嘌呤二核苷酸（NAD）结合结构域和C端的糖酵解结构域。检查了位于N-末端结构域的该李斯特菌蛋白的推定ADP-核糖基化能力，并且显示出与铜绿假单胞菌ExoS在内体-内体融合上施加的活性和Rab 5a抑制的一些相似性。李斯特菌p40引起Rab 5a特异性ADP核糖基化并阻断Rab 5a交换因子（Vps 9）和GDI的相互作用和功能，解释了在Rab 5a介导的吞噬体-内体融合中观察到的抑制作用。同时，ExoS破坏Rab 5-早期内体抗原1（EEA 1）的相互作用，并显示出更广泛的Rab特异性。李斯特菌GAPDH可能是第一个具有ADP-核糖基化能力的革兰氏阳性酶，是一种新的毒力因子。
Listeria monocytogenes (LM) phagocytic strategy implies recruitment and inhibition of Rab5a. Here, we identify a Listeria protein that binds to Rab5a and is responsible for Rab5a recruitment to phagosomes and impairment of the GDP/GTP exchange activity. This protein was identified as a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Listeria (p40 protein, Lmo 2459). The p40 protein was found within the phagosomal membrane. Analysis of the sequence of LM p40 protein revealed two enzymatic domains: the nicotinamide adenine dinucleotide (NAD)-binding domain at the N-terminal and the C-terminal glycolytic domain. The putative ADP-ribosylating ability of this Listeria protein located in the N-terminal domain was examined and showed some similarities to the activity and Rab5a inhibition exerted by Pseudomonas aeruginosa ExoS onto endosome-endosome fusion. Listeria p40 caused Rab5a-specific ADP ribosylation and blocked Rab5a-exchange factor (Vps9) and GDI interaction and function, explaining the inhibition observed in Rab5a-mediated phagosome-endosome fusion. Meanwhile, ExoS impaired Rab5-early endosomal antigen 1 (EEA1) interaction and showed a wider Rab specificity. Listeria GAPDH might be the first intracellular gram-positive enzyme targeted to Rab proteins with ADP-ribosylating ability and a putative novel virulence factor.