Fong Jessica H, Shoemaker Benjamin A, Garbuzynskiy Sergiy O, Lobanov Michail Y, Galzitskaya Oxana V, Panchenko Anna R
National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Comput Biol. 2009 Mar;5(3):e1000316. doi: 10.1371/journal.pcbi.1000316. Epub 2009 Mar 13.
We perform a large-scale study of intrinsically disordered regions in proteins and protein complexes using a non-redundant set of hundreds of different protein complexes. In accordance with the conventional view that folding and binding are coupled, in many of our cases the disorder-to-order transition occurs upon complex formation and can be localized to binding interfaces. Moreover, analysis of disorder in protein complexes depicts a significant fraction of intrinsically disordered regions, with up to one third of all residues being disordered. We find that the disorder in homodimers, especially in symmetrical homodimers, is significantly higher than in heterodimers and offer an explanation for this interesting phenomenon. We argue that the mechanisms of regulation of binding specificity through disordered regions in complexes can be as common as for unbound monomeric proteins. The fascinating diversity of roles of disordered regions in various biological processes and protein oligomeric forms shown in our study may be a subject of future endeavors in this area.
我们使用一组由数百种不同蛋白质复合物组成的非冗余集，对蛋白质和蛋白质复合物中的内在无序区域进行了大规模研究。根据折叠和结合相互关联的传统观点，在我们研究的许多案例中，无序到有序的转变发生在复合物形成时，并且可以定位到结合界面。此外，对蛋白质复合物中无序情况的分析表明，相当一部分区域是内在无序的，所有残基中多达三分之一处于无序状态。我们发现，同二聚体中的无序，尤其是对称同二聚体中的无序，明显高于异二聚体，并对这一有趣现象给出了解释。我们认为，通过复合物中无序区域调节结合特异性的机制，可能与未结合的单体蛋白一样普遍。我们研究中展示的无序区域在各种生物过程和蛋白质寡聚形式中所起的迷人多样的作用，可能是该领域未来研究的主题。
