NMR structure of a receptor-bound G-protein peptide

• Published in: Nature (London) 1993-05, Vol.363 (6426), p.276-281
• Main Authors: Dratz, Edward A, Furstenau, Julie E, Lambert, Christophe G, Thireault, Dennis L, Rarick, Helen, Schepers, Theresa, Pakhlevaniants, Sergei, Hamm, Heidi E
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biochemistry; Biological and medical sciences; Cellular biology; conformation; Fundamental and applied biological sciences. Psychology; guanine nucleotide-binding protein; Humanities and Social Sciences; Interactions. Associations; Intermolecular phenomena; letter; Light; Magnetic Resonance Spectroscopy; membranes; Models, Molecular; Molecular biophysics; Molecular Sequence Data; multidisciplinary; N.M.R; NMR; Nuclear magnetic resonance; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - radiation effects; Protein Conformation; Proteins; receptors; rhodopsin; Rhodopsin - chemistry; Rhodopsin - metabolism; Rhodopsin - radiation effects; Science; Science (multidisciplinary); structure; transducin; Transducin - chemistry; Transducin - metabolism; Transducin - radiation effects
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/363276a0

HETEROTRIMERIC GTP-binding proteins (G proteins) regulate cellular activity by coupling to hormone or sensory receptors. Stimulated receptors catalyse the release of GDP from G protein α-subunits 1–4 and GTP bound to the empty α-subunits provides signals that control effectors such as adenylyl cyclases, phos-phodiesterases, phospholipases and ion channels 4 . Three cytoplas-mic loops of the activated receptor are thought to interact with three sites on the heterotrimeric G protein to provide high-affinity interaction and catalyse G-protein activation 5–8 . The carboxyl terminus of the α-subunit is particularly important for interaction with the receptor 9–14 . Here we study the structure of part of the active interface between the photon receptor rhodopsin and the G protein transducin, or G t , using nuclear magnetic resonance. An 11-amino-acid peptide from the C terminus of the α-summit of G t (α t (340–350)) binds to rhodopsin and mimics the G protein in stabilizing its active form, metarhodopsin II. The peptide α t (340–350) binds to both excited and unexcited rhodopsin and conformational differences between the two bound forms suggest a mechanism for activation of G proteins by agonist-stimulated receptors. Insight into receptor-catalysed GDP release will have broad application because the GTP/GDP exchange and the intrinsic GTPase activity of GTP-binding proteins constitute a widespread regulatory mechanism 15 .