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Titolo:
Structural mimicry in G protein-coupled receptors: Implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors
Autore:
Ballesteros, JA; Shi, L; Javitch, JA;
Indirizzi:
Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Novasite Pharmaceut Inc, San Diego, CA USA Novasite Pharmaceut Inc San Diego CA USA armaceut Inc, San Diego, CA USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 1, volume: 60, anno: 2001,
pagine: 1 - 19
SICI:
0026-895X(200107)60:1<1:SMIGPR>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
SITE-DIRECTED MUTAGENESIS; MEMBRANE-SPANNING SEGMENT; BETA-ADRENERGIC-RECEPTOR; DOPAMINE D2 RECEPTOR; LIGHT-DEPENDENT CHANGES; LIGAND-BINDING SITE; CYSTEINE ACCESSIBILITY METHOD; TRANSMEMBRANE ALPHA-HELICES; TACHYKININ NK-1 RECEPTOR; DISULFIDE CROSS-LINKING;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
128
Recensione:
Indirizzi per estratti:
Indirizzo: Javitch, JA Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, P&S 11-401,630 W 168th St, New York, NY 10032 USA Columbia Univ Coll Phys & Surg P&S 11-401,630 W 168th St New York NY USA 10032
Citazione:
J.A. Ballesteros et al., "Structural mimicry in G protein-coupled receptors: Implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors", MOLEC PHARM, 60(1), 2001, pp. 1-19

Abstract

The availability of a high-resolution structure of rhodopsin now allows usto reconsider research attempts to understand structure-function relationships in other G protein-coupled receptors (GPCRs). A comparison of the rhodopsin structure with the results of previous sequence analysis and molecular modeling that incorporated experimental results demonstrates a high degree of success for these methods in predicting the helix ends and protein-protein interface of GPCRs. Moreover, the amino acid residues inferred to formthe surface of the binding-site crevice based on our application of the substituted-cysteine accessibility method in the dopamine D-2 receptor are inremarkable agreement with the rhodopsin structure, with the notable exception of some residues in the fourth transmembrane segment. Based on our analysis of the data reviewed, we propose that the overall structures of rhodopsin and of amine receptors are very similar, although we also identified localized regions where the structure of these receptors may diverge. We further propose that several of the highly unusual structural features of rhodopsin are also present in amine GPCRs, despite the absence of amino acids that might have thought to have been critical to the adoption of these features. Thus, different amino acids or alternate microdomains can support similar deviations from regular or-helical structure, thereby resulting in similar tertiary structure. Such structural mimicry is a mechanism by which a common ancestor could diverge sufficiently to develop the selectivity necessary to interact with diverse signals, while still maintaining a similar overall fold. Through this process, the core function of signaling activation through a conformational change in the transmembrane segments that alters the conformation of the cytoplasmic surface and subsequent interaction with Gproteins is presumably shared by the entire Class A family of receptors, despite their selectivity for a diverse group of ligands.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 07:22:33