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Titolo:
Three-dimensional structure of human follicle-stimulating hormone
Autore:
Fox, KM; Dias, JA; Van Roey, P;
Indirizzi:
New York State Dept Hlth, Wadsworth Ctr Labs & Res, Div Mol Med, Albany, NY 12201 USA New York State Dept Hlth Albany NY USA 12201 ol Med, Albany, NY 12201 USA Union Coll, Dept Chem, Schenectady, NY 12308 USA Union Coll Schenectady NY USA 12308 Dept Chem, Schenectady, NY 12308 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 3, volume: 15, anno: 2001,
pagine: 378 - 389
SICI:
0888-8809(200103)15:3<378:TSOHFH>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CHORIONIC-GONADOTROPIN; ALPHA-SUBUNIT; RECEPTOR-BINDING; BETA-SUBUNIT; HUMAN CHORIOGONADOTROPIN; HUMAN FOLLITROPIN; AMINO-ACIDS; GLYCOPROTEIN HORMONES; CRYSTAL-STRUCTURE; TERMINAL REGION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Van Roey, P New York State Dept Hlth, Wadsworth Ctr Labs & Res, Div Mol Med, POB 509, Albany, NY 12201 USA New York State Dept Hlth POB 509 Albany NYUSA 12201 12201 USA
Citazione:
K.M. Fox et al., "Three-dimensional structure of human follicle-stimulating hormone", MOL ENDOCR, 15(3), 2001, pp. 378-389

Abstract

The crystal structure of a beta Thr26Ala mutant of human follicle-stimulating hormone (hFSH) has been determined to 3.0 Angstrom resolution. The hFSHmutant was expressed in baculovirus-infected Hi5 insect cells and purifiedby affinity chromatography, using a beta hFSH-specific monoclonal antibody. The beta Thr26Ala mutation results in elimination of the beta Asn24 glycosylation site, yielding protein more suitable for crystallization without affecting the receptor binding and signal transduction activity of the glycohormone. The crystal structure has two independent hFSH molecules in the asymmetric unit and a solvent content of about 80%. The alpha -and beta subunits of hFSH have similar folds, consisting of central cystine-knot motifs from which three beta -hairpins extend. The two subunits associate very tightly in a head-to-tail arrangement, forming an elongated, slightly curved structure, similar to that of human chorionic gonadotropin (hCG). The hFSH heterodimers differ only in the conformations of the amino and carboxy termini and the second loop of the beta -subunit (L2 beta). Detailed comparison of the structures of hFSH and hCG reveals several differences in the beta -subunits that may be important with respect to receptor binding specificity or signal transduction. These differences include conformational changes and/or differential distributions of polar or charged residues in loops L3 beta (hFSH residues 62-73), the cystine noose, or determinant loop (residues 87-94), and the carboxy-terminal loop (residues 94-104). An additional interesting feature of the hFSH structure is an extensive hydrophobic patch in the area formed by loops alpha L1, alpha L3, and beta L2. Glycosylation at alpha Asn52 is well known to be required for full signal transduction activity and heterodimer stability. The structure reveals an intersubunit hydrogen bonding interaction between this carbohydrate and beta Tyr58, an indication of a mechanism by which the carbohydrate may stabilize the heterodimer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:37:11