CNRS UMR 7258, INSERM U 1068, Centre de Recherche en Cancérologie de Marseille, Marseille F-13009, France.
FEBS Lett. 2012 Jun 21;586(13):1759-64. doi: 10.1016/j.febslet.2012.05.017. Epub 2012 May 26.
The functions of Src family kinases are tightly regulated through Src homology (SH) domain-mediated protein-protein interactions. We previously reported the biophysical characteristics of the apoptosis-linked gene 2-interacting protein X (Alix) in complex with the haemopoietic cell kinase (Hck) SH3 domain. In the current study, we have combined ITC, NMR, SAXS and molecular modeling to determine a 3D model of the complex. We demonstrate that Hck SH3 recognizes an extended linear proline-rich region of Alix. This particular binding mode enables Hck SH3 to sense a specific non-canonical residue situated in the SH3 RT-loop of the kinase. The resulting model helps clarify the mechanistic insights of Alix-Hck interaction.
Src 家族激酶的功能通过Src 同源（SH）结构域介导的蛋白-蛋白相互作用来严格调控。我们之前曾报道过凋亡相关基因 2 相互作用蛋白 X（Alix）与造血细胞激酶（Hck）SH3 结构域复合物的生物物理特性。在本研究中，我们结合了 ITC、NMR、SAXS 和分子建模来确定复合物的 3D 模型。我们证明 Hck SH3 识别 Alix 的一个扩展线性富含脯氨酸的区域。这种特殊的结合模式使 Hck SH3 能够感知激酶 SH3 RT 环中位于特定非典型残基的信号。所得到的模型有助于阐明 Alix-Hck 相互作用的机制见解。
