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Titolo:
Dimerization and domain swapping in g-protein-coupled receptors: A computational study
Autore:
Gouldson, PR; Higgs, C; Smith, RE; Dean, MK; Gkoutos, GV; Reynolds, CA;
Indirizzi:
Dept Biol Sci, Colchester CO4 3SQ, Essex, England Dept Biol Sci Colchester Essex England CO4 3SQ er CO4 3SQ, Essex, England
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 4, volume: 23, anno: 2000, supplemento:, S
pagine: S60 - S77
SICI:
0893-133X(200010)23:4<S60:DADSIG>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC MUSCARINIC RECEPTORS; SITE-DIRECTED MUTAGENESIS; 3 DIFFERENT STATES; MOLECULAR-DYNAMICS SIMULATIONS; CHOLECYSTOKININ CCK RECEPTOR; BETA(2) ADRENERGIC-RECEPTOR; SH-SY5Y NEUROBLASTOMA-CELLS; LIGAND-BINDING SPECIFICITY; TRANSCRIPT CLEAVAGE FACTOR; EVOLUTIONARY TRACE METHOD;
Keywords:
activation; adrenergic; bioinformatics; Brownian dynamics; correlated mutation analysis; dimerization; domain swapping; domains; evolutionary trace analysis; functional rescue; G protein; G protein-coupled receptors; GPCR; molecular dynamics; molecular modelling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
132
Recensione:
Indirizzi per estratti:
Indirizzo: Reynolds, CA Dept Biol Sci, Cent Campus,Wivenhoe Pk, Colchester CO4 3SQ, Essex, England Dept Biol Sci Cent Campus,Wivenhoe Pk Colchester Essex England CO4 3SQ
Citazione:
P.R. Gouldson et al., "Dimerization and domain swapping in g-protein-coupled receptors: A computational study", NEUROPSYCH, 23(4), 2000, pp. S60-S77

Abstract

In recent years there has been an increasing number of reports describing G protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the evidence on the nature of the dimers and their role in GPCR activation is inconclusive. Consequently, we present here a review of our computational studies on G protein-coupled receptor dimerization and domain swapping. The studies described include molecular dynamics simulations on receptor monomers and dimers in the absence of ligand, in the presence of an agonist, and in the presence of an antagonist (or more precisely an inverse agonist). Two distinct sequence-based approaches to studying protein interfacesare also described, namely correlated mutation analysis and evolutionary trace analysis. AII three approaches concur in supporting the proposal that the dimerization interface includes transmembrane helices 5 and 6. These studies cannot distinguish between domain swapped dimers and contact dimers as the models used were restricted to the helical part of the receptor. However, it is proposed that for the purpose of signalling, the domain swapped dimer and the corresponding contact dimer are equivalent. The evolutionary trace analysis suggests that every GPCR family and subfamily (for which sufficient sequence data is available) has the potential to dimerize through this common functional site on helices 5 and 6. The evolutionary trace results on the G protein are briefly described and these are consistent with GPCR dimerization. In addition to the functional site on helices 5 and 6, the evolutionary trace analysis identified a second functional site on helices 2 and 3. Possible roles for this site are suggested, including oligomerization. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

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Documento generato il 05/12/20 alle ore 20:19:06