Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5G 1L6, Canada.
Nat Commun. 2018 Oct 31;9(1):4549. doi: 10.1038/s41467-018-06943-2.
Src homology 2 (SH2) domains play a critical role in signal transduction in mammalian cells by binding to phosphorylated Tyr (pTyr). Apart from a few isolated cases in viruses, no functional SH2 domain has been identified to date in prokaryotes. Here we identify 93 SH2 domains from Legionella that are distinct in sequence and specificity from mammalian SH2 domains. The bacterial SH2 domains are not only capable of binding proteins or peptides in a Tyr phosphorylation-dependent manner, some bind pTyr itself with micromolar affinities, a property not observed for mammalian SH2 domains. The Legionella SH2 domains feature the SH2 fold and a pTyr-binding pocket, but lack a specificity pocket found in a typical mammalian SH2 domain for recognition of sequences flanking the pTyr residue. Our work expands the boundary of phosphotyrosine signalling to prokaryotes, suggesting that some bacterial effector proteins have acquired pTyr-superbinding characteristics to facilitate bacterium-host interactions.
Src 同源结构域 2（SH2）通过与磷酸化的 Tyr（pTyr）结合，在哺乳动物细胞的信号转导中发挥着关键作用。除了病毒中有少数孤立的情况外，目前在原核生物中尚未发现具有功能的 SH2 结构域。在这里，我们从军团菌中鉴定出 93 个 SH2 结构域，它们在序列和特异性上与哺乳动物 SH2 结构域明显不同。这些细菌 SH2 结构域不仅能够以 Tyr 磷酸化依赖性的方式结合蛋白质或肽，有些还以微摩尔亲和力结合 pTyr 本身，这是哺乳动物 SH2 结构域所没有的特性。军团菌 SH2 结构域具有 SH2 折叠和 pTyr 结合口袋，但缺乏典型的哺乳动物 SH2 结构域中用于识别 pTyr 残基侧翼序列的特异性口袋。我们的工作将磷酸酪氨酸信号转导的范围扩展到了原核生物，表明一些细菌效应蛋白已经获得了 pTyr 超结合特性，以促进细菌-宿主的相互作用。
