Decorin binds fibrinogen in a Zn2+-dependent interaction.
We have previously shown that decorin, a member of the small leucine-rich proteoglycan family of extracellular matrix proteoglycans/glycoproteins is a Zn(2+) metalloprotein at physiological Zn(2+) concentrations (Yang, V. W-C., LaBrenz, S. R., Rosenberg, L. C., McQuillan, D., and Höök, M. (1999) J. Biol. Chem. 274, 12454-12460). We now report that the decorin proteoglycan binds fibrinogen in the presence of Zn(2+). The fibrinogen-binding site is located in the N-terminal domain of the decorin core protein and a 45-amino acid peptide representing this domain binds to the fibrinogen D fragment with an apparent K(D) of 1.7 x 10(-6) m, as determined from fluorescence polarization data. Furthermore, we show that Zn(2+) promotes the self-association of decorin. The N-terminal domain of the core protein also mediates this activity. The results of solid-phase binding assays and gel filtration chromatography suggest that the N-terminal domain of decorin, when present at low micromolar concentrations, forms an oligomer in a Zn(2+)-dependent manner. Thus, Zn(2+) appears to play a pivotal role in the interactions and biological function of decorin.
Dugan
Tracey A
TA
Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas Medical Center, Houston 77030, USA.
Yang
Vivian W-C
VW
McQuillan
David J
DJ
Höök
Magnus
M
D000818:Animals; D001665:Binding Sites; D019921:Biotinylation; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D058575:Decorin; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D010455:Peptides; D011509:Proteoglycans; D011994:Recombinant Proteins; D005340:Fibrinogen; D015032:Zinc