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Titolo:
A PROPOSED STRUCTURE FOR TRANSMEMBRANE SEGMENT-7 OF G-PROTEIN-COUPLEDRECEPTORS INCORPORATING AN ASN-PRO ASP-PRO MOTIF/
Autore:
KONVICKA K; GUARNIERI F; BALLESTEROS JA; WEINSTEIN H;
Indirizzi:
CUNY MT SINAI SCH MED,DEPT PHYSIOL & BIOPHYS,1 GUSTAVE L LEVY PL,BOX 1218 NEW YORK NY 10029 CUNY MT SINAI SCH MED,DEPT PHYSIOL & BIOPHYS NEW YORK NY 10029
Titolo Testata:
Biophysical journal
fascicolo: 2, volume: 75, anno: 1998,
pagine: 601 - 611
SICI:
0006-3495(1998)75:2<601:APSFTS>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEMBRANE-SPANNING SEGMENT; BINDING-SITE CREVICE; GONADOTROPIN-RELEASING-HORMONE; TACHYKININ NK-1 RECEPTOR; F LOOP REGION; ADRENERGIC-RECEPTOR; CONFORMATIONAL MEMORIES; 3-DIMENSIONAL STRUCTURE; MOLECULAR MECHANICS; MUTATIONAL ANALYSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
65
Recensione:
Indirizzi per estratti:
Citazione:
K. Konvicka et al., "A PROPOSED STRUCTURE FOR TRANSMEMBRANE SEGMENT-7 OF G-PROTEIN-COUPLEDRECEPTORS INCORPORATING AN ASN-PRO ASP-PRO MOTIF/", Biophysical journal, 75(2), 1998, pp. 601-611

Abstract

Transmembrane segment (TMS) 7 has been shown to play an important role in the signal transduction function of G-protein-coupled receptors (GPCRs). Although transmembrane segments are most likely to adopt a helical structure, results from a variety of experimental studies involving TMS 7 are inconsistent with it being an ideal alpha-helix. Using results from a search of the structure database and extensive simulated annealing Monte Carlo runs with the new Conformational Memories method, we have identified the conserved (N/D)PxxY region of TMS 7 as the major determinant for deviation of TMS 7 from ideal helicity. The perturbation consists of an Asx turn and a flexible ''hinge'' region. The Conformational Memories procedure yielded a model structure of TMS 7 which, unlike an ideal alpha-helix, is capable of accommodating all of the experimentally derived geometrical criteria for the interactions of TMS 7 in the transmembrane bundle of GPCRs. In the context of the entire structure of a transmembrane bundle model for the 5HT(2a) receptor,the specific perturbation of TMS 7 by the NP sequence suggests a structural hypothesis for the pattern of amino acid conservation observed in TMS 1, 2, and 7 of GPCRs. The structure resulting from the incorporation of the (N/D)P motif satisfies fully the H-bonding capabilities of the 100% conserved polar residues in these TMSs, in agreement with results from mutagenesis experiments. The flexibility introduced by thespecific structural perturbation produced by the (NP/DP) motif in TMS7 is proposed to have a significant role in receptor activation.

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Documento generato il 28/11/20 alle ore 01:01:17