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Titolo:
On the spatial disposition of the fifth transmembrane helix and the structural integrity of the transmembrane binding site in the opioid and ORL1 G protein-coupled receptor family
Autore:
Topham, CM; Mouledous, L; Meunier, JC;
Indirizzi:
Inst Pharmacol & Biol Struct, CNRS UPR 9062, Unite Neuropharmacol Mol, F-31077 Toulouse 4, France Inst Pharmacol & Biol Struct Toulouse France 4 -31077 Toulouse 4, France
Titolo Testata:
PROTEIN ENGINEERING
fascicolo: 7, volume: 13, anno: 2000,
pagine: 477 - 490
SICI:
0269-2139(200007)13:7<477:OTSDOT>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINE D2 RECEPTOR; HUMAN ALPHA(2A)-ADRENERGIC RECEPTOR; MEMBRANE-SPANNING SEGMENT; ORPHANIN FQ RECEPTOR; DIRECTED MUTAGENESIS; LIGAND-BINDING; AMINO-ACIDS; PROJECTION STRUCTURE; CONSERVED ASPARTATE; SIGNAL-TRANSDUCTION;
Keywords:
amino acid sequence cluster analysis; annotation of function; nociceptin; opioid and amine G protein-coupled receptors; rhodopsin molecular modelling; site-directed mutagenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
87
Recensione:
Indirizzi per estratti:
Indirizzo: Topham, CM Inst Pharmacol & Biol Struct, CNRS UPR 9062, Unite Neuropharmacol Mol, 205Route Narbonne, F-31077 Toulouse 4, France Inst Pharmacol & BiolStruct 205 Route Narbonne Toulouse France 4
Citazione:
C.M. Topham et al., "On the spatial disposition of the fifth transmembrane helix and the structural integrity of the transmembrane binding site in the opioid and ORL1 G protein-coupled receptor family", PROTEIN ENG, 13(7), 2000, pp. 477-490

Abstract

sequence alignment of G protein-coupled receptor seven-helix folds supports the existence of structurally conserved transmembrane (TM) ligand bindingsites in the opioid/opioid receptor-like (ORL1) and amine receptor families. Based on the expectation that functionally conserved regions in homologous proteins will display locally higher levels of sequence identity compared with global sequence similarities that pertain to the overall fold, this approach may have wider applications in functional genomics to annotate sequence data. Binding sites in models of the kappa-opioid receptor seven-helix bundle built from the rhodopsin templates of Baldwin et al. (1997) [J, Mol, Biol., 272, 1.44-164] and Herzyk and Hubbard (1998) [J, MoE, Biol., 281,742-751] are compared. The Herzyk and Hubbard template is found to be in better accord with experimental studies of amine, opioid and rhodopsin receptors owing to the reduced physical separation of the extracellular parts ofTM helices V and VI and differences in the rotational orientation of the N-terminal of helix V that reveal side chain accessibilities in the Baldwin et al, structure to be out of phase with relative alkylation rates of engineered cysteine residues in the TM binding site of the alpha(2A)-adrenergic receptor. TM helix V in the Baldwin ef al. template has been remodelled with a different proline kink to satisfy experimental constraints. A recent proposal that rotation of helix V is associated with receptor activation is critically discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/02/20 alle ore 20:01:50