Jaeger Werner C, Armstrong Stephen P, Hill Stephen J, Pfleger Kevin D G
Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia , Perth, WA , Australia.
Cell Signalling Research Group, School of Life Sciences, Queen's Medical Centre, University of Nottingham Medical School , Nottingham , UK.
Front Endocrinol (Lausanne). 2014 Mar 5;5:26. doi: 10.3389/fendo.2014.00026. eCollection 2014.
Guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) function in complexes with a range of molecules and proteins including ligands, G proteins, arrestins, ubiquitin, and other receptors. Elements of these complexes may interact constitutively or dynamically, dependent upon factors such as ligand binding, phosphorylation, and dephosphorylation. They may also be allosterically modulated by other proteins in a manner that changes temporally and spatially within the cell. Elucidating how these complexes function has been greatly enhanced by biophysical technologies that are able to monitor proximity and/or binding, often in real time and in live cells. These include resonance energy transfer approaches such as bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). Furthermore, the use of fluorescent ligands has enabled novel insights into allosteric interactions between GPCRs. Consequently, biophysical approaches are helping to unlock the amazing diversity and bias in G protein-coupled receptor signaling.
鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体（GPCRs）与一系列分子和蛋白质形成复合物发挥作用，这些分子和蛋白质包括配体、G蛋白、抑制蛋白、泛素及其他受体。这些复合物的组成部分可能会持续或动态地相互作用，这取决于诸如配体结合、磷酸化和去磷酸化等因素。它们也可能会被其他蛋白质以在细胞内随时间和空间变化的方式进行变构调节。能够监测接近度和/或结合情况（通常是实时监测活细胞中的情况）的生物物理技术极大地促进了对这些复合物功能的阐释。这些技术包括共振能量转移方法，如生物发光共振能量转移（BRET）和荧光共振能量转移（FRET）。此外，荧光配体的使用使人们对GPCRs之间的变构相互作用有了新的认识。因此，生物物理方法有助于揭示G蛋白偶联受体信号传导中惊人的多样性和偏向性。
