Institut de Biologie Structurale, Université Grenoble 1 , 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
Biochemistry. 2013 Sep 10;52(36):6160-8. doi: 10.1021/bi400363v. Epub 2013 Aug 26.
Src homology 3 (SH3) domains are widely known for their ability to interact with other proteins using the canonical PxxP binding motif. Besides those well-characterized interaction modes, there is an increasing number of SH3 domain-containing complexes that lack this motif. Here we characterize the interaction of SH3 domains, in particular the Bin1-SH3 domain, with the intrinsically disordered part of nonstructural protein 5A of the hepatitis C virus using noncanonical binding sites in addition to its PxxP motif. These binding regions partially overlap with regions that have previously been identified as having an increased propensity to form α-helices. Remarkably, upon interaction with the Bin1-SH3 domain, the α-helical propensity decreases and a fuzzy complex is formed.
Src 同源结构域 3（SH3）以其使用典型的 PxxP 结合基序与其他蛋白质相互作用的能力而广为人知。除了这些特征明确的相互作用模式外，还有越来越多缺乏这种基序的 SH3 结构域包含复合物。在这里，我们使用丙型肝炎病毒非结构蛋白 5A 的无规卷曲部分的非典型结合位点来描述 SH3 结构域，特别是 Bin1-SH3 结构域的相互作用，除了其 PxxP 基序之外。这些结合区域与以前确定的具有增加形成α-螺旋倾向的区域部分重叠。值得注意的是，与 Bin1-SH3 结构域相互作用后，α-螺旋倾向降低，形成模糊复合物。
