title: Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy.
abstract: G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the conformational changes that are essential for activation remains largely unanswered. Since the extracellular sequences and structures of GPCRs are not conserved between receptor subfamilies, it is likely that the initial molecular triggers for activation vary depending on the specific type of ligand and receptor. In this article, we describe NMR studies on the rhodopsin subfamily of GPCRs and propose a mechanism for how retinal isomerization switches the receptor to the active conformation. These results suggest a general approach for determining the triggers for activation in other GPCR subfamilies using NMR spectroscopy.
authors: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, United States.
authors: Naoki
authors: N
authors: Kimata
authors: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, United Kingdom.
authors: Philip J
authors: PJ
authors: Reeves
authors: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, United States. Electronic address: steven.o.smith@stonybrook.edu.
authors: Steven O
authors: SO
authors: Smith
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001665:Binding Sites; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000648:ultrastructure; D012243:Rhodopsin / Q000737:chemistry* / Q000648:ultrastructure*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin
keywords: G protein-coupled receptor; Magic angle spinning; Solid-state NMR spectroscopy