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Titolo:
Three-dimensional structural analysis of fibronectin heparin-binding domain mutations
Autore:
Kapila, Y; Doan, D; Tafolla, E; Fletterick, R;
Indirizzi:
Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
, , anno: 2001, supplemento:, 36
pagine: 156 - 161
SICI:
0730-2312(2001):<156:TSAOFH>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
GINGIVAL CREVICULAR FLUID; SYNOVIAL-FLUID; V-REGION; FRAGMENTS; CHONDROLYSIS; PROTEINASES; EXPRESSION; CELLS;
Keywords:
fibronectin; heparin-binding domain; point mutations; modeling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
12
Recensione:
Indirizzi per estratti:
Indirizzo: Kapila, Y Univ Calif San Francisco, Dept Stomatol, HSW 604,Box 0512, San Francisco, CA 94143 USA Univ Calif San Francisco HSW 604,Box 0512 San Francisco CA USA 94143
Citazione:
Y. Kapila et al., "Three-dimensional structural analysis of fibronectin heparin-binding domain mutations", J CELL BIOC, 2001, pp. 156-161

Abstract

Using recombinant fibronectin proteins containing the V region and two paint mutations in the high-affinity heparin-binding domain, Lye previously showed that these domains modulate tumor cell invasion as well as proteinase expression and apoptosis in human fibroblasts. Structurally, the wildtype counterparts to these two point mutations, together with four other discontinuous, positively charged residues, form a cationic cradle in domain III-13of fibronectin that binds heparin. We constructed a three-dimensional model of this cationic cradle and determined whether the two engineered point mutations in the heparin-binding domain would alter this cradle conformation, thus explaining the altered cell behavior. Our model of fibronectin domain III-13 was generated from a template of the three-dimensional structure of a homologous (25% identity) domain, III-3, from tenascin. The amino acid sequences of III-13 that differed from tenascin III-3 were replaced, and side chains for positively charged arginines 6 and 7 were substituted with uncharged threonines. The model revealed that the two mutated threonine residues were solvent accessible, readily accommodated as part of an antiparallel beta strand, and remained part of the three-dimensional cradle. These models suggest that the two point mutations in the heparin-binding domain of fibronectin III-13 alter cell function probably through changes in charge and not through changes in the conformational structure of the cationic cradle, (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 18:22:17