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Nature:能被大肠杆菌转位的一种蛋白的结构被确定

2011/01/06 来源:Nature 中文
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导读
大肠杆菌的致病菌种将很多蛋白转位进宿主细胞中,以促进其毒性。这些蛋白中的其中一个(来自大肠杆菌O157:H7的EspG)的结构,已在与两个宿主酶形成的一个复合物中被确定,其机制也已被弄清。这些结构揭示了EspG是怎样通过在膜细胞器上的囊泡萌芽反应期间有针对性地识别宿主ARF6酶的

大肠杆菌的致病菌种将很多蛋白转位进宿主细胞中,以促进其毒性。这些蛋白中的其中一个(来自大肠杆菌O157:H7的EspG)的结构,已在与两个宿主酶形成的一个复合物中被确定,其机制也已被弄清。这些结构揭示了EspG是怎样通过在膜细胞器上的囊泡萌芽反应期间有针对性地识别宿主ARF6酶的与GTP结合的活性状态来破坏内膜运输通道的。EspG是直接激发PAK激酶的,其方式是束缚该激酶激发级联中一个未折叠的过渡态。

 

原文出处:

Nature doi:10.1038/nature09593

The assembly of a GTPase–kinase signalling complex by a bacterial catalytic scaffold

Andrey S. Selyunin,Sarah E. Sutton,Bethany A. Weigele,L. Evan Reddick,Robert C. Orchard,Stefan M. Bresson,Diana R. Tomchick" Neal M. Alto

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits1, 2. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components3, 4, 5, 6. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding7, 8, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5?? crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8?? crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a ‘catalytic scaffold’ that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.

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