Department of Bioengineering, School of Engineering , The University of Tokyo , 7-3-1, Hongo , Bunkyo-ku, Tokyo 113-8656 , Japan.
The Institute of Medical Science , The University of Tokyo , 4-6-1, Shirokanedai , Minato-ku, Tokyo 108-8639 , Japan.
Biochemistry. 2019 Feb 12;58(6):504-508. doi: 10.1021/acs.biochem.8b01194. Epub 2019 Jan 14.
The affinity of a ligand for a receptor on the cell surface will be influenced by the membrane composition. Herein, we evaluated the effects of differences in membrane fluidity, controlled by phospholipid composition, on the ligand binding activity of the G protein-coupled receptor human serotonin 2B. Using Nanodisc technology to control membrane properties, we performed biophysical analysis and employed molecular dynamics simulations to demonstrate that increased membrane fluidity shifted the equilibrium toward an active form of the receptor. Our quantitative study will enable development of more realistic in vitro drug discovery assays involving membrane-bound proteins such as G protein-coupled receptors.
配体与细胞表面受体的亲和力将受到膜组成的影响。在此，我们评估了通过磷脂组成控制的膜流动性差异对 G 蛋白偶联受体人血清素 2B 的配体结合活性的影响。使用 Nanodisc 技术控制膜性质，我们进行了生物物理分析，并采用分子动力学模拟证明了增加膜流动性会使平衡向受体的活跃形式转移。我们的定量研究将能够开发更现实的体外药物发现测定法，涉及膜结合蛋白，如 G 蛋白偶联受体。
