Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor.
Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor.
复制标题
Src SH2 结构域与 PDGF β 受体激活形式相互作用的结构和热力学基础。
DOI：
10.1016/s0022-2836(03)00344-9
复制
发表时间：
2003
影响因子：
5.6
通讯作者：
Waksman,Gabriel
中科院分区：
文献类型：
--
作者：
Lubman,OlgaY;Waksman,Gabriel
Src激酶向血小板衍生生长因子（PDGF）受体的活化形式的募集涉及通过酶的Src同源2（SH2）结构域识别受体的质膜区域中的独特序列基序。该基序含有两个磷酸酪氨酸残基，由一个残基隔开（序列pYIpYV，其中pY表示磷酸酪氨酸）。在这里，我们提供的热力学和结构基础的结合，这个主题的Src SH2结构域。我们表明，第二次磷酸化事件增加了自由能窗口特定的相互作用和生理目标是精心设计的任务，专门招募SH2域，否则表现出非常小的内在能力，以区分序列的C-末端的第一个磷酸化事件。令人惊讶的是，我们发现水在识别过程中发挥了作用。
Recruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process.