Differential dynamics in the G protein-coupled receptor rhodopsin revealed by solution NMR.
G protein-coupled receptors are cell-surface seven-helical membrane proteins that undergo conformational changes on activation. The mammalian photoreceptor, rhodopsin, is the best-studied member of this superfamily. Here, we provide the first evidence that activation in rhodopsin may involve differential dynamic properties of side-chain versus backbone atoms. High-resolution NMR studies of alpha-(15)N-labeled receptor revealed large backbone motions in the inactive dark state. In contrast, indole side-chain (15)N groups of tryptophans showed well resolved, equally intense NMR signals, suggesting restriction to a single specific conformation.
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Judith
J
Klein-Seetharaman
Naveena V K
NV
Yanamala
Fathima
F
Javeed
Philip J
PJ
Reeves
Elena V
EV
Getmanova
Michele C
MC
Loewen
Harald
H
Schwalbe
H Gobind
HG
Khorana
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D009587:Nitrogen Isotopes; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014364:Tryptophan; D012243:Rhodopsin