SH2域
化学
蛋白质-蛋白质相互作用
结合位点
计算生物学
半胱氨酸
原癌基因酪氨酸蛋白激酶Src
血浆蛋白结合
生物化学
立体化学
信号转导
生物物理学
生物
酶
作者
Rui Wang,Pete Y. M. Leung,Feng Huang,Qingzhuang Tang,Tomonori Kaneko,Mei Huang,Zigang Li,Shawn S.‐C. Li,Yi Wang,Junfeng Xia
出处
期刊:Biochemistry
[American Chemical Society]
日期:2018-08-09
卷期号:57 (35): 5257-5269
被引量:7
标识
DOI:10.1021/acs.biochem.8b00677
摘要
Discerning the different interaction states during dynamic protein-ligand binding is difficult. Here we apply site-specific cysteine-α-chloroacetyl cross-linking to scrutinize the binding between the Src homology 2 (SH2) domain and phosphotyrosine (pY) peptides, a highly dynamic interaction that is a key to cellular signal transduction. From a model SH2 protein to a set of representative SH2 domains, we showed here that a proximity-induced cysteine-α-chloroacetyl reaction cross-linked two spatially adjacent chemical groups as a result of the binding interaction, and reciprocally, the information about the interaction states can be deduced from the cross-linked products. To our surprise, we found SH2 domains can adopt a reverse binding mode with "single-pronged", "two-pronged", and "half" pY peptides. This finding was further supported by a set of 500 ns molecular dynamics simulations. This serendipitous finding defies the canonical theory of SH2 binding, suggests a possible answer about the source of the versatility of SH2 signaling, and sets a model for other protein binding interactions.
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