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Titolo:
A new method to model membrane protein structure based on silent amino acid substitutions
Autore:
Briggs, JAG; Torres, J; Arkin, IT;
Indirizzi:
Univ Cambridge, Dept Biochem, Cambridge Ctr Mol Recognit, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW nit, Cambridge CB2 1QW, England
Titolo Testata:
PROTEINS-STRUCTURE FUNCTION AND GENETICS
fascicolo: 3, volume: 44, anno: 2001,
pagine: 370 - 375
SICI:
0887-3585(20010815)44:3<370:ANMTMM>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMEMBRANE ALPHA-HELICES; ZETA-CHAIN DIMERIZATION; CELL ANTIGEN RECEPTOR; STRUCTURE PREDICTION; HOMOLOGOUS PROTEINS; SECONDARY STRUCTURE; PHOSPHOLAMBAN; SEQUENCES; DOMAIN; ASSOCIATION;
Keywords:
membrane proteins; CD3-zeta; glycophorin; molecular dynamics; proteomics; molecular modeling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Arkin, IT Hebrew Univ Jerusalem, Dept Biol Chem, Alexander Silberman Inst Life Sci, Givat Ram, IL-91904 Jerusalem, Israel Hebrew Univ Jerusalem GivatRam Jerusalem Israel IL-91904 srael
Citazione:
J.A.G. Briggs et al., "A new method to model membrane protein structure based on silent amino acid substitutions", PROTEINS, 44(3), 2001, pp. 370-375

Abstract

The importance of accurately modeling membrane proteins cannot be overstated, in lieu of the difficulties in solving their structures experimentally. Often, however, modeling procedures (e.g., global searching molecular dynamics) generate several possible candidates rather then pointing to a singlemodel. Herein we present a new approach to select among candidate models based on the general hypothesis that silent amino acid substitutions, present in variants identified from evolutionary conservation data or mutagenesisanalysis, do not affect the stability of a native structure but may destabilize the non-native structures also found. The proof of this hypothesis has been tested on the alpha -helical transmembrane domains of two homodimers, human glycophorin A and human CD3-zeta, a component of the T-cell receptor. For both proteins, only one structure was identified using all the variants. For glycophorin A, this structure is virtually identical to the structure determined experimentally by NAM. We present a model for the transmembrane domain of CD3-zeta that is consistent with predictions based on mutagenesis, homology modeling, and the presence of a disulfide bond. Our experiments suggest that this method allows the prediction of transmembrane domain structure based only on widely available evolutionary conservation data. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 23:42:57