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Titolo:
Partial restoration of lutropin activity by an intersubunit disulfide bond: Iimplications for structure/function studies
Autore:
Einstein, M; Lin, W; Macdonald, GJ; Moyle, WR;
Indirizzi:
Robert Wood Johnson Med Sch, Dept Obstet & Gynecol, Piscataway, NJ 08854 USA Robert Wood Johnson Med Sch Piscataway NJ USA 08854 cataway, NJ 08854 USA Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA Robert Wood Johnson Med Sch Piscataway NJ USA 08854 cataway, NJ 08854 USA
Titolo Testata:
EXPERIMENTAL BIOLOGY AND MEDICINE
fascicolo: 6, volume: 226, anno: 2001,
pagine: 581 - 590
SICI:
1535-3702(200106)226:6<581:PROLAB>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CHORIONIC-GONADOTROPIN; ALPHA-SUBUNIT; HUMAN CHORIOGONADOTROPIN; GLYCOPROTEIN HORMONES; BETA-SUBUNIT; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; PROTEIN; DOMAIN;
Keywords:
LH receptor; FSH receptor; hCG; bifunctional gonadotropins; crosslinked hCG analogs;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Moyle, WR Robert Wood Johnson Med Sch, Dept Obstet & Gynecol, 675 Hoes Lane, Piscataway, NJ 08854 USA Robert Wood Johnson Med Sch 675 Hoes Lane Piscataway NJ USA 08854
Citazione:
M. Einstein et al., "Partial restoration of lutropin activity by an intersubunit disulfide bond: Iimplications for structure/function studies", EXP BIOL ME, 226(6), 2001, pp. 581-590

Abstract

Gonadal function is controlled by lutropins and follitropins, heterodimeric cystine knot proteins that have nearly identical alpha -subunits. These heterodimeric proteins are stabilized by a portion of the hormone-specific beta -subunit termed the "seatbelt" that is wrapped around alpha -subunit loop 2 (alpha2), Here we show that replacing human chorionic gonadotropin (hCG) (alpha2 residue Lys51 with cysteine or alanine nearly abolished its lutropin activity, an observation that implies that alpha Lys51 has a key role in hormone activity. The activity of the heterodimer containing alpha K51C,but not that containing (alpha K51A, was increased substantially when beta-subunit seatbelt residue beta Asp99 was converted to cysteine, As had been reported by others, heterodimers containing (alpha K51C and beta D99C were crosslinked by a disulfide. The finding that an intersubunit disulfide restored some of the activity lost by replacing alpha Lys51 suggests that this residue is not crucial for receptor binding or signaling and also that hCG and related hormones may be particularly sensitive to mutations that alter interactions between their subunits. We propose the unique structures of hCG and related family members may permit some subunit movement in the heterodimer, making it difficult to deduce key residues involved in receptor contacts simply by correlating the activities of hormone analogs with their amino acid sequences.

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Documento generato il 17/01/20 alle ore 21:06:50