BioNMR Laboratory, Inorganic and Organic Chemistry Department, Universitat de Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2, 34092 Montpellier, France; Instituto de Tecnologia Química e Biológica António Xavier, ITQB NOVA, Avenida da República, 2780-157 Oeiras, Portugal.
Structure. 2017 Apr 4;25(4):630-640.e4. doi: 10.1016/j.str.2017.02.011. Epub 2017 Mar 16.
The N-terminal regulatory region of c-Src including the SH4, Unique, and SH3 domains adopts a compact, yet highly dynamic, structure that can be described as an intramolecular fuzzy complex. Most of the long-range interactions within the Unique domain are also observed in constructs lacking the structured SH3, indicating a considerable degree of preorganization of the disordered Unique domain. Here we report that members of the Src family of kinases (SFK) share well-conserved sequence features involving aromatic residues in their Unique domains. This observation contrasts with the supposed lack of sequence homology implied by the name of these domains and suggests that the other members of SFK also have a regulatory region involving their Unique domains. We argue that the Unique domain of each SFK is sensitive to specific input signals, encoded by each specific sequence, but the entire family shares a common mechanism for connecting the disordered and structured domains.
c-Src 的 N 端调节区包含 SH4、Unique 和 SH3 结构域，形成一个紧凑但高度动态的结构，可以被描述为分子内的模糊复合物。Unique 结构域内的大多数远程相互作用也存在于缺乏结构化 SH3 的构建体中，这表明无序的 Unique 结构域具有相当程度的预组织。在这里，我们报告说 Src 家族激酶 (SFK) 的成员共享保守的序列特征，涉及它们 Unique 结构域中的芳香族残基。这一观察结果与这些结构域名称所暗示的序列同源性缺乏形成对比，表明 SFK 的其他成员也具有涉及它们的 Unique 结构域的调节区。我们认为，每个 SFK 的 Unique 结构域对每个特定序列编码的特定输入信号敏感，但整个家族共享一种将无序和结构化结构域连接起来的通用机制。
