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A 49-Residue Peptide from Adhesin F1 of Streptococcus pyogenesInhibits Fibronectin Matrix Assembly*

Authors :
Tomasini-Johansson, Bianca R.
Kaufman, Nicole R.
Ensenberger, Martin G.
Ozeri, Vered
Hanski, Emanuel
Mosher, Deane F.
Source :
Journal of Biological Chemistry; June 2001, Vol. 276 Issue: 26 p23430-23439, 10p
Publication Year :
2001

Abstract

F1 is an adhesin of Streptococcus pyogeneswhich binds the N-terminal 70-kDa region of fibronectin with high affinity. The fibronectin binding region of F1 is comprised of a 43-residue upstream domain and a repeat domain comprised of five tandem 37-residue sequences. We investigated the effects of these domains on the assembly of fibronectin matrix by human dermal fibroblasts, MG63 osteosarcoma cells, or fibroblasts derived from fibronectin-null stem cells. Subequimolar or equimolar concentrations of recombinant proteins containing both the upstream and repeat domains or just the repeat domain enhanced binding of fibronectin or its N-terminal 70-kDa fragment to cell layers; higher concentrations of these recombinant proteins inhibited binding. The enhanced binding did not result in greater matrix assembly and was caused by increased ligand binding to substratum. In contrast, recombinant or synthetic protein containing the 43 residues of the upstream domain and the first 6 residues from the repeat domain exhibited monophasic inhibition with an IC50of ∼10 nm. Truncation of the 49-residue sequence at its N or C terminus caused loss of inhibitory activity. The 49-residue upstream sequence blocked incorporation of both endogenous cellular fibronectin and exogenous plasma fibronectin into extracellular matrix and inhibited binding of 70-kDa fragment to fibronectin-null cells in a fibronectin-free system. Inhibition of matrix assembly by the 49-mer had no effect on cell adhesion to substratum, cell growth, formation of focal contacts, or formation of stress fibers. These results indicate that the 49-residue upstream sequence of F1 binds in an inhibitory mode to N-terminal parts of exogenous and endogenous fibronectin which are critical for fibronectin fibrillogenesis.

Details

Language :
English
ISSN :
00219258 and 1083351X
Volume :
276
Issue :
26
Database :
Supplemental Index
Journal :
Journal of Biological Chemistry
Publication Type :
Periodical
Accession number :
ejs7173075
Full Text :
https://doi.org/10.1074/jbc.M103467200