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Titolo:
Similar structures and shared switch mechanisms of the beta(2)-adrenoceptor and the parathyroid hormone receptor - Zn(II) bridges between helices IIIand VI block activation
Autore:
Sheikh, SP; Vilardarga, JP; Baranski, TJ; Lichtarge, O; Iiri, T; Meng, EC; Nissenson, RA; Bourne, HR;
Indirizzi:
Univ94143f San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CAUniv Calif San Francisco San Francisco CA USA 94143 ol, San Francisco, CA UnivCAalif San Francisco, Endocrine Unit, Dept Vet Affairs, San Francisco,Univ Calif San Francisco San Francisco CA USA 94143 fairs, San Francisco,
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 24, volume: 274, anno: 1999,
pagine: 17033 - 17041
SICI:
0021-9258(19990611)274:24<17033:SSASSM>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-COUPLED RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; BETA-ADRENERGIC RECEPTORS; TACHYKININ NK-1 RECEPTOR; ADENYLATE-CYCLASE; TRANSMEMBRANE HELICES; SYNTHETIC PEPTIDES; RHODOPSIN MUTANTS; LYMPHOMA-CELLS; ALPHA-SUBUNIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Bourne, HR S1212,Box 0450,513 Parnassus Ave, San Francisco, CA 94143 USA S1212,Box 0450,513 Parnassus Ave San Francisco CA USA 94143 SA
Citazione:
S.P. Sheikh et al., "Similar structures and shared switch mechanisms of the beta(2)-adrenoceptor and the parathyroid hormone receptor - Zn(II) bridges between helices IIIand VI block activation", J BIOL CHEM, 274(24), 1999, pp. 17033-17041

Abstract

The seven transmembrane helices of serpentine receptors comprise a conserved switch that relays signals from extracellular stimuli to heterotrimeric G proteins on the cytoplasmic face of the membrane. By substituting histidines for residues at the cytoplasmic ends of helices III and VI in retinal rhodopsin, we engineered a metal-binding site whose occupancy by Zn(II) prevented the receptor from activating a retinal G protein, G(t) (Sheikh, S. P., Zvyaga, T. A., Lichtarge, O., Sakmar, T. P., and Bourne, H. R. (1996) Nature 383, 347-350), Now we report engineering of metal-binding sites bridging the cytoplasmic ends of these two helices in two other serpentine receptors, the beta(2)-adrenoreceptor and the parathyroid hormone receptor; occupancy of the metal-binding site by Zn(II) markedly impairs the ability of each receptor to mediate ligand-dependent activation of G(s), the stimulatory regulator of adenylyl cyclase, We infer that these two receptors share withrhodopsin a common three-dimensional architecture and an activation switchthat requires movement, relative to one another, of helices III and VI; these inferences are surprising in the case of the parathyroid hormone receptor, a receptor that contains seven stretches of hydrophobic sequence but whose amino acid sequence otherwise shows no apparent similarity to those of receptors in the rhodopsin family. These findings highlight the evolutionary conservation of the switch mechanism of serpentine receptors and help to constrain models of how the switch works.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 01:00:44