Miyanabe Kazuhiro, Yamashita Takefumi, Abe Yoshito, Akiba Hiroki, Takamatsu Yuichiro, Nakakido Makoto, Hamakubo Takao, Ueda Tadashi, Caaveiro Jose M M, Tsumoto Kouhei
Department of Chemistry and Biotechnology, School of Engineering , The University of Tokyo , 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-8656 , Japan.
Laboratory for Systems Biology and Medicine, RCAST , The University of Tokyo , 4-6-1 Komaba , Meguro-ku, Tokyo 153-8904 , Japan.
Biochemistry. 2018 Jul 17;57(28):4177-4185. doi: 10.1021/acs.biochem.8b00592. Epub 2018 Jul 5.
Protein tyrosine sulfation (PTS) is a post-translational modification regulating numerous biological events. PTS generally occurs at flexible regions of proteins, enhancing intermolecular interactions between proteins. Because of the high flexibility associated with the regions where PTS is generally encountered, an atomic-level understanding has been difficult to achieve by X-ray crystallography or nuclear magnetic resonance techniques. In this study, we focused on the conformational behavior of a flexible sulfated peptide and its interaction with an antibody. Molecular dynamics simulations and thermodynamic analysis indicated that PTS reduced the main-chain fluctuations upon the appearance of sulfate-mediated intramolecular H-bonds. Collectively, our data suggested that one of the mechanisms by which PTS may enhance protein-protein interactions consists of the limitation of conformational dynamics in the unbound state, thus reducing the loss of entropy upon binding and boosting the affinity for its partner.
蛋白质酪氨酸硫酸化（PTS）是一种调节众多生物学事件的翻译后修饰。PTS通常发生在蛋白质的柔性区域，增强蛋白质之间的分子间相互作用。由于与PTS通常出现的区域相关的高柔性，通过X射线晶体学或核磁共振技术很难实现原子水平的理解。在本研究中，我们关注一种柔性硫酸化肽的构象行为及其与抗体的相互作用。分子动力学模拟和热力学分析表明，PTS在硫酸盐介导的分子内氢键出现时减少了主链波动。总体而言，我们的数据表明，PTS增强蛋白质-蛋白质相互作用的机制之一包括限制未结合状态下的构象动力学，从而减少结合时的熵损失并提高对其伴侣的亲和力。
