BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
Structure. 2015 May 5;23(5):893-902. doi: 10.1016/j.str.2015.03.009. Epub 2015 Apr 23.
Regulation of c-Src activity by the intrinsically disordered Unique domain has recently been demonstrated. However, its connection with the classical regulatory mechanisms is still missing. Here we show that the Unique domain is part of a long loop closed by the interaction of the SH4 and SH3 domains. The conformational freedom of the Unique domain is further restricted through direct contacts with SH3 that are allosterically modulated by binding of a poly-proline ligand in the presence and in the absence of lipids. Our results highlight the scaffolding role of the SH3 domain for the c-Src N-terminal intrinsically disordered regions and suggest a connection between the regulatory mechanisms involving the SH3 and Unique domains.
最近已经证明，c-Src 活性受固有无序独特域的调节。然而，其与经典调节机制的联系仍然缺失。在这里，我们表明独特域是由 SH4 和 SH3 结构域相互作用封闭的长环的一部分。独特域的构象自由度进一步受到与 SH3 的直接接触限制，这种接触通过在存在和不存在脂质的情况下与多脯氨酸配体结合而变构调节。我们的结果突出了 SH3 结构域在 c-Src N 端无规卷曲区域中的支架作用，并表明涉及 SH3 和独特域的调节机制之间存在联系。
