Institute of Molecular Genetics National Research Council, Pavia, Italy.
PLoS One. 2011;6(11):e27789. doi: 10.1371/journal.pone.0027789. Epub 2011 Nov 14.
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.
禽流感（AI）病毒的非结构蛋白 1（NS1）对于致病性很重要。在这里，我们在一组全球流行的 AI 病毒的 NS1 蛋白的极端羧基末端鉴定出一个以前未被识别的串联 PDZ-配体（TPL）结构域。通过使用蛋白质阵列，我们已经鉴定出该新型结构域的几种人类 PDZ-细胞配体，其中之一是 RIL 蛋白，它是已知的细胞酪氨酸激酶Src 的调节剂。我们发现 AI NS1 蛋白通过其羧基末端Src 同源性类型 3 结合（SHB）结构域与人类Src 酪氨酸激酶结合并刺激其活性。NS1 与 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，AI NS1 蛋白的 TPL 和 SHB 结构域可能介导新的宿主-病原体相互作用。
