The EHEC-host interactome reveals novel targets for the translocated intimin receptor.
The EHEC-host interactome reveals novel targets for the translocated intimin receptor.
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DOI：
10.1038/srep07531
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发表时间：
2014-12-18
影响因子：
4.6
通讯作者：
Koegl M
中科院分区：
文献类型：
--
作者：
Blasche S;Arens S;Ceol A;Siszler G;Schmidt MA;Häuser R;Schwarz F;Wuchty S;Aloy P;Uetz P;Stradal T;Koegl M
肠出血性大肠大肠杆菌（EHEC）通过至少39种效应蛋白操纵其人类宿主，这些效应蛋白通过直接蛋白质-蛋白质相互作用（PPI）劫持宿主过程。为了确定它们在宿主细胞中的蛋白质靶点，我们进行了酵母双杂交筛选，使我们能够在15种EHEC效应物和47种人类宿主蛋白质之间找到48种高置信度的蛋白质-蛋白质相互作用。与其他细菌和病毒相比，我们发现EHEC效应子更频繁地与中心蛋白以及参与更多蛋白质复合物的蛋白质结合。该数据集包括六种涉及易位的内膜受体（TIR）的新相互作用，即HPCAL 1，HPCAL 4，NCALD，ARRB 1，PDE 6D和STK 16。我们比较了EHEC和肠致病性E. coli（EPEC）中，发现有5种相互作用是保守的。值得注意的是，保守的相互作用包括丝氨酸/苏氨酸激酶16（STK 16）、神经钙蛋白样1（HPCAL 1）以及神经钙蛋白-δ（NCALD）的相互作用。这些蛋白质与EPEC的感染位点共定位。此外，我们的研究结果表明，推定的功能不佳的特征效应（EspJ，EspY 1）。特别是，我们观察到EspJ连接到微管系统，而EspY 1似乎参与细胞凋亡/细胞周期调节。
Enterohemorrhagic E. coli (EHEC) manipulate their human host through at least 39 effector proteins which hijack host processes through direct protein-protein interactions (PPIs). To identify their protein targets in the host cells, we performed yeast two-hybrid screens, allowing us to find 48 high-confidence protein-protein interactions between 15 EHEC effectors and 47 human host proteins. In comparison to other bacteria and viruses we found that EHEC effectors bind more frequently to hub proteins as well as to proteins that participate in a higher number of protein complexes. The data set includes six new interactions that involve the translocated intimin receptor (TIR), namely HPCAL1, HPCAL4, NCALD, ARRB1, PDE6D, and STK16. We compared these TIR interactions in EHEC and enteropathogenic E. coli (EPEC) and found that five interactions were conserved. Notably, the conserved interactions included those of serine/threonine kinase 16 (STK16), hippocalcin-like 1 (HPCAL1) as well as neurocalcin-delta (NCALD). These proteins co-localize with the infection sites of EPEC. Furthermore, our results suggest putative functions of poorly characterized effectors (EspJ, EspY1). In particular, we observed that EspJ is connected to the microtubule system while EspY1 appears to be involved in apoptosis/cell cycle regulation.
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