The PDZ-Ligand and Src-Homology Type 3 Domains of Epidemic Avian Influenza Virus NS1 Protein Modulate Human Src Kinase Activity during Viral Infection
The PDZ-Ligand and Src-Homology Type 3 Domains of Epidemic Avian Influenza Virus NS1 Protein Modulate Human Src Kinase Activity during Viral Infection
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DOI：
10.1371/journal.pone.0027789
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发表时间：
2011-11-14
期刊：
影响因子：
3.7
通讯作者：
Maga, Giovanni
中科院分区：
文献类型：
--
作者：
Bavagnoli, Laura;Dundon, William G.;Maga, Giovanni
禽流感病毒的非结构蛋白1（NS 1）对禽流感病毒的致病性具有重要作用。在这里，我们确定了一个以前未被识别的串联PDZ配体（TPL）结构域在极端的羧基末端的NS 1蛋白从一个子集的全球流行的AI病毒。通过使用蛋白质阵列，我们已经确定了几个人PDZ-细胞配体的这种新的域，其中之一是RIL蛋白，细胞酪氨酸激酶Src的一种已知的调节剂。我们发现AI NS 1蛋白通过其羧基末端Src同源3型结合（SHB）结构域结合并刺激人Src酪氨酸激酶。NS 1和Src之间的物理相互作用以及AI病毒在感染过程中调节Src磷酸化状态的能力被发现受到TPL排列的影响。这些结果表明，由AI NS 1蛋白的TPL和SHB结构域介导的新型宿主-病原体相互作用的潜力。
The Non-structural 1 (NS1) protein of avian influenza (AI) viruses is important for pathogenicity. Here, we identify a previously unrecognized tandem PDZ-ligand (TPL) domain in the extreme carboxy terminus of NS1 proteins from a subset of globally circulating AI viruses. By using protein arrays we have identified several human PDZ-cellular ligands of this novel domain, one of which is the RIL protein, a known regulator of the cellular tyrosine kinase Src. We found that the AI NS1 proteins bind and stimulate human Src tyrosine kinase, through their carboxy terminal Src homology type 3-binding (SHB) domain. The physical interaction between NS1 and Src and the ability of AI viruses to modulate the phosphorylation status of Src during the infection, were found to be influenced by the TPL arrangement. These results indicate the potential for novel host-pathogen interactions mediated by the TPL and SHB domains of AI NS1 protein.