Park Minyoung, Sivertsen Bjørn B, Els-Heindl Sylvia, Huber Thomas, Holst Birgitte, Beck-Sickinger Annette G, Schwartz Thue W, Sakmar Thomas P
Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, The Panum Institute, Blegdamsvej 3b, 2200 Copenhagen, Denmark.
Chem Biol. 2015 Nov 19;22(11):1431-1436. doi: 10.1016/j.chembiol.2015.09.014. Epub 2015 Nov 5.
Ghrelin receptor (GhrR) is a promising drug target because of its central role in energy homeostasis. GhrR, known for high constitutive activity, is thought to display multi-state conformations during activation and signaling. We used genetically encoded unnatural amino acids and bioorthogonal labeling reactions to engineer multiple fluorescent donor-acceptor pairs to probe ligand-directed structural changes in GhrR. We demonstrate how conformational dynamics of a G-protein-coupled receptor can be measured in reconstituted systems.
胃饥饿素受体（GhrR）因其在能量平衡中的核心作用而成为一个有前景的药物靶点。GhrR以高组成性活性而闻名，被认为在激活和信号传导过程中呈现多态构象。我们使用基因编码的非天然氨基酸和生物正交标记反应来构建多个荧光供体-受体对，以探测GhrR中配体导向的结构变化。我们展示了如何在重构系统中测量G蛋白偶联受体的构象动力学。
