The Unique Domain Forms a Fuzzy Intramolecular Complex in Src Family Kinases
The Unique Domain Forms a Fuzzy Intramolecular Complex in Src Family Kinases
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DOI：
10.1016/j.str.2017.02.011
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发表时间：
2017-04-04
期刊：
影响因子：
5.7
通讯作者：
Pons, Miquel
中科院分区：
文献类型：
--
作者：
Arbesu, Miguel;Maffei, Mariano;Pons, Miquel
C-Src的N-末端调控区包括SH4、Unique和SH3结构域，采用了一种紧凑但高度动态的结构，可以描述为分子内模糊复合体。唯一结构域中的大多数远程相互作用也在缺乏结构化SH3的结构中观察到，这表明无序的唯一结构域有相当程度的预组织。在此，我们报道了在其独特的结构域中，含有芳香族残基的Src蛋白家族(SFK)成员具有非常保守的序列特征。这一观察结果与这些结构域的名称所暗示的缺乏序列同源性的假设形成了对比，并表明SFK的其他成员也有一个涉及其独特结构域的调节区。我们认为，每个SFK的独特结构域对特定的输入信号敏感，由每个特定的序列编码，但整个家族共享一个连接无序和结构化结构域的共同机制。
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.