Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands.
Int J Mol Sci. 2014 May 6;15(5):7841-64. doi: 10.3390/ijms15057841.
Agonist binding is related to a series of motions in G protein-coupled receptors (GPCRs) that result in the separation of transmembrane helices III and VI at their cytosolic ends and subsequent G protein binding. A large number of smaller motions also seem to be associated with activation. Most helices in GPCRs are highly irregular and often contain kinks, with extensive literature already available about the role of prolines in kink formation and the precise function of these kinks. GPCR transmembrane helices also contain many α-bulges. In this article we aim to draw attention to the role of these α-bulges in ligand and G-protein binding, as well as their role in several aspects of the mobility associated with GPCR activation. This mobility includes regularization and translation of helix III in the extracellular direction, a rotation of the entire helix VI, an inward movement of the helices near the extracellular side, and a concerted motion of the cytosolic ends of the helices that makes their orientation appear more circular and that opens up space for the G protein to bind. In several cases, α-bulges either appear or disappear as part of the activation process.
激动剂结合与一系列 G 蛋白偶联受体 (GPCR) 分子的运动有关，这些运动导致跨膜螺旋 III 和 VI 在胞质末端分离，随后与 G 蛋白结合。大量较小的运动似乎也与激活有关。GPCR 中的大多数螺旋高度不规则，通常包含扭结，关于脯氨酸在扭结形成中的作用以及这些扭结的精确功能，已经有大量文献。GPCR 跨膜螺旋还包含许多 α-凸起。在本文中，我们旨在强调这些 α-凸起在配体和 G 蛋白结合中的作用，以及它们在与 GPCR 激活相关的几个方面的运动中的作用。这种运动包括螺旋 III 在细胞外方向上的规则化和平移、整个螺旋 VI 的旋转、靠近细胞外侧的螺旋向内运动，以及螺旋胞质末端的协调运动，使它们的方向看起来更圆，并为 G 蛋白的结合腾出空间。在几种情况下，α-凸起作为激活过程的一部分出现或消失。
