Huang Yongqi, Liu Zhirong
State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Int J Mol Sci. 2011 Feb 23;12(2):1410-30. doi: 10.3390/ijms12021410.
Anchor residues, which are deeply buried upon binding, play an important role in protein-protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs) which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17-Asn29, abbreviated as p53N) which are involved in binding with two different targets (MDM2 and Taz2), and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex). We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs).
在结合时被深埋的锚定残基，通过提供识别特异性和促进结合动力学，在蛋白质-蛋白质相互作用中发挥重要作用。到目前为止，对锚定残基的研究主要集中在有序蛋白质上。在本研究中，我们研究了在自由状态下具有柔性的内在无序蛋白质（IDP）中的锚定残基。我们鉴定了p53蛋白N端（Glu17-Asn29，简称为p53N）中与两种不同靶标（MDM2和Taz2）结合的锚定残基，并分析了它们在未结合状态下的侧链构象。发现未结合的p53N中的锚定残基经常采样与结合复合物中观察到的构象相似的构象（即p53N-MDM2复合物中的Phe19、Trp23和Leu26，以及p53N-Taz2复合物中的Leu22）。我们认为，未结合状态下锚定残基的类似结合构象对于控制IDP与其靶标之间的特异性相互作用很重要。此外，我们提出了一种机制，从锚定残基和分子识别特征（MoRF）方面解释IDP的结合多特异性。
