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Titolo:
ENHANCED FOLDING AND PROCESSING OF A DISULFIDE MUTANT OF THE HUMAN ASIALOGLYCOPROTEIN RECEPTOR H2B SUBUNIT
Autore:
YUK MH; LODISH HF;
Indirizzi:
WHITEHEAD INST BIOMED RES,9 CAMBRIDGE CTR CAMBRIDGE MA 02142 WHITEHEAD INST BIOMED RES CAMBRIDGE MA 02142 MIT,DEPT BIOL CAMBRIDGE MA 02139
Titolo Testata:
The Journal of biological chemistry
fascicolo: 34, volume: 270, anno: 1995,
pagine: 20169 - 20176
SICI:
0021-9258(1995)270:34<20169:EFAPOA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HEPATOMA-CELLS; ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; BINDING PROTEINS; BOND FORMATION; PRE-GOLGI; SEQUENCE; CALCIUM; POLYPEPTIDES; SECRETION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
M.H. Yuk e H.F. Lodish, "ENHANCED FOLDING AND PROCESSING OF A DISULFIDE MUTANT OF THE HUMAN ASIALOGLYCOPROTEIN RECEPTOR H2B SUBUNIT", The Journal of biological chemistry, 270(34), 1995, pp. 20169-20176

Abstract

Unfolded forms of the H2b subunit of the human asialoglycoprotein receptor, a galactose-specific C-type lectin, are degraded in the endoplasmic reticulum (ER), whereas folded forms of the protein can mature tothe cell surface (Wikstrom, L., and Lodish, H. F. (1993) J. Biol. Chem. 268, 14412-14416). There are eight cysteines in the exoplasmic domain of the protein, forming four disulfide bonds in the folded protein,We have constructed double cysteine to alanine mutants for each of the four disulfide bonds and examined the folding and metabolic fate of each of the mutants in transfected 3T3 fibroblasts, We find that mutation of the two cysteines nearest to the transmembrane region (C1) doesnot prevent proper folding of the protein, whereas mutations of the other three disulfides prevent proper folding of the protein and all ofthe mutant proteins are degraded in the ER, A normal (similar to 20%)fraction of the C1 mutant protein exits the endoplasmic reticulum andis processed in the Gels complex, and it does so at a faster rate compared to the wild-type, Furthermore, the folded form of this mutant protein is more resistant to unfolding by dithiothreitol than the wild-type. The CI mutant protein is expressed on the cell surface and can form a functional receptor with the H1 subunit with similar binding affinities for natural ligands as that of the wild-type receptor, The samefraction of newly made mutant and wild-type proteins (similar to 80%)remain in the ER, but the mutant protein is degraded more quickly, Thus, the presence of the C1 disulfide bond in the wild-type receptor both reduces the rate of protein folding and exit to the Golgi and slowsthe rate of ER degradation of the portion (similar to 80%) of the receptor that never folds properly.

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Documento generato il 11/07/20 alle ore 17:42:27