Mallik Saurav, Ray Tanaya, Kundu Sudip
Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, India.
Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase-II), University of Calcutta, India.
FEBS Lett. 2017 Jul;591(14):2180-2191. doi: 10.1002/1873-3468.12725. Epub 2017 Jul 8.
Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing.
许多生物蛋白质在其末端表现出内在无序性，这与多种功能作用相关。在此，我们展示了一个惊人的结果，即具有增强柔韧性的末端短瞬态无序区域（TstDREF）百分比增加与球状蛋白质的加速折叠速率相关。TstDREF处预测无序性的进化保守性以及点突变时折叠速率的剧烈改变表明TstDREF在塑造折叠动力学中起关键调节作用。TstDREF与长程分子内相互作用相关，并且TstDREF物理接触的天然二级结构元件百分比与折叠动力学呈现出另一种惊人的正相关。这些结果使我们能够推断TstDREF介导的折叠动力学调节背后可能的分子机制，这促使蛋白质生物化学家通过直接实验测试进行评估。
