Kimata Naoki, Pope Andreyah, Sanchez-Reyes Omar B, Eilers Markus, Opefi Chikwado A, Ziliox Martine, Reeves Philip J, Smith Steven O
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
School of Biological Sciences, University of Essex, Essex, UK.
Nat Struct Mol Biol. 2016 Aug;23(8):738-43. doi: 10.1038/nsmb.3257. Epub 2016 Jul 4.
Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins.
G蛋白偶联受体（GPCRs）跨膜螺旋中的保守脯氨酸通常被认为起到铰链的作用，将螺旋分为能够独立运动的两个部分。根据其形成氢键的潜力，与这些脯氨酸相关的游离C=O基团可以促进受体结构的构象灵活性、构象转换或稳定。为了通过固态核磁共振光谱研究保守脯氨酸在A类GPCRs中的作用，我们聚焦于牛视紫红质，它是视觉受体亚家族中的一种GPCR。H5和H7螺旋上的游离主链C=O基团通过与相邻螺旋上的残基形成氢键来稳定无活性的视紫红质结构。响应于视黄醛发色团的光诱导异构化，涉及这些C=O基团的氢键相互作用被释放，从而促进H5和H7重新排列到受体的跨膜核心上。这些结果为脯氨酸在膜蛋白中的多种结构和功能作用提供了见解。
