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Titolo:
CALCIUM STABILIZES FIBRILLIN-1 AGAINST PROTEOLYTIC DEGRADATION
Autore:
REINHARDT DP; ONO RN; SAKAI LY;
Indirizzi:
SHRINERS HOSP CRIPPLED CHILDRENS PORTLAND OR 97201 OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOL BIOL PORTLAND OR 97201
Titolo Testata:
The Journal of biological chemistry
fascicolo: 2, volume: 272, anno: 1997,
pagine: 1231 - 1236
SICI:
0021-9258(1997)272:2<1231:CSFAPD>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEONATAL MARFAN-SYNDROME; FACTOR-LIKE DOMAINS; AMINO-ACID SEQUENCE; DEPENDENT PROTEIN-S; EGF-LIKE REPEATS; HUMAN FACTOR-IX; DROSOPHILA-NOTCH; EXTRACELLULAR-MATRIX; FIBROBLAST-CULTURES; BINDS CALCIUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
D.P. Reinhardt et al., "CALCIUM STABILIZES FIBRILLIN-1 AGAINST PROTEOLYTIC DEGRADATION", The Journal of biological chemistry, 272(2), 1997, pp. 1231-1236

Abstract

The calcium binding epidermal growth factor (cbEGF)-like domain is a structural motif that is present in many matrix proteins throughout the animal kingdom from invertebrates to mammals, This module has been demonstrated to bind calcium in the micromolar range. However, little is known about the functional consequences of calcium binding to proteins that contain this structural element. We used fibrillin-1, an extracellular matrix protein consisting of similar to 60% cbEGF-like motifs, as a model system to study stabilizing effects of calcium in protease degradation assays. Authentic human fibrillin-1 and recombinant human fibrillin-1 subdomains, spanning the whole molecule, showed significantly slower proteolytic degradation in the presence of CaCl2 than in the presence of EDTA, demonstrating that calcium stabilizes the structure of fibrillin-1 and protects the molecule against proteolytic degradation. Information about cleavage sites protected by calcium was obtained with a new recombinant subdomain, rF17 (Asp(952)-Val(1527)), comprising the longest stretch of cbEGF-like motifs in the center of the fibrillin-1 molecule. The most sensitive sites for trypsin and endoproteinase Glu-C were observed in cbEGF-like motifs 11 (Met(1034) and Asn(1046)), 12 (Ser(1103)), and 17 (Thr(1318)). Since most of the currently known mutations in fibrillin-1 are found within cbEGF-like motifs and are predicted to disrupt calcium binding, we suggest that these mutations render fibrillin-1 more susceptible to proteolytic cleavage, andthis might be one of the reasons why these mutations result in Marfan's syndrome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 16:29:23