Decorin Is a Zn2+ Metalloprotein

Abstract

Decorin is ubiquitously distributed in the extracellular matrix of mammals and a member of the proteoglycan family characterized by a core protein dominated by leucine-rich repeat motifs. We show here that decorin extracted from bovine tissues under denaturing conditions or produced in recombinant "native" form by cultured mammalian cells has a high affinity for Zn 2؉ Decorin, a small chondroitin/dermatan sulfate proteoglycan, is found in the extracellular matrix of a variety of tissues such as skin (1-3), cartilage (4, 5), and bone (6, 7). This proteoglycan is composed of a 40-kDa core protein and one glycosaminoglycan chain attached to a serine residue in the N-terminal part of the protein. The decorin core protein is dominated by a central region composed of 10 leucine-rich repeat units. Each unit contains 21-26 amino acid residues and is proposed to adopt a characteristic ␣-helix/␤-sheet folding pattern (8, 9). The C-and N-terminal regions of the core protein are believed to form globular structures stabilized by disulfide bonds between sets of cysteine residues. Several proteoglycans have core proteins of similar size and structural organization. These related molecules are considered to form a family called small leucine-rich proteoglycans (SLRP) 1 (9, 10). The family of SLRPs include decorin, biglycan, and epiphycan, all of which contain chondroitin/dermatan sulfate chains attached to the N-terminal domain of the core protein and fibromodulin, lumican, keratocan, PRELP, and osteoglycin which often have keratan sulfate linked to asparagine residues in the central region of the core protein.The extracellular matrix glycoprotein chondroadherin has a structural organization similar to the core proteins of the SLRPs but has not been shown to be substituted with glycosaminoglycan chains (11). The biological importance of the different SLRPs is unclear. In vitro binding studies have shown that decorin, biglycan, and fibromodulin can interact with several types of collagen (12-16) and different SLRPs are believed to be important regulators of collagen fibrillogenesis. In support of this hypothesis, a decorin-deficient mouse was found to have fragile skin with an abnormal organization of collagen fibers (17). The phenotype appears to be largely restricted to the skin, perhaps suggesting that other SLRPs have similar functions and may fulfill this role in other collagenous tissues.In fact, a lumican-deficient mouse also exhibited abnormal collagen fibers both in the skin and cornea (18). Decorin may also affect the production of other extracellular matrix components by regulating the activity of transforming growth factor-␤ (19,20). Additionally, decorin can modulate the interactions of matrix molecules such as fibronectin with cells (21-23). These observations suggest that decorin and perhaps other SLRPs regulate at several levels the production and assembly of the extracellular matrix and hence the remodeling of connective tissue.Zinc, a divalent cation, is one of the essential trace elements for eukaryotic org...

Decorin Core Protein Secretion Is Regulated by N-Linked Oligosaccharide and Glycosaminoglycan Additions

“…Expression of Decorin and Decorin Fragments in Escherichia coli-The cloning, expression, and purification of full-length decorin as an MBP fusion protein (MBP-decorin), and of a decorin N-terminal peptide as a GST fusion protein (GST-MD4) and the production of the isolated peptide (MD4) have been described previously (23).…”

“…1). Recombinant decorin core protein and core protein fragments were expressed as fusion proteins in E. coli, as previously described (23). Control peptides of MBP and GST alone were also purified.…”

Decorin suppresses tumor cell-mediated angiogenesis

“…It has been shown that several basement membrane proteins, such as laminin and type IV collagen, directly induce the formation of capillary-like structures in endothelial cells, whereas fragments of these molecules inhibit the process (Sage, 1997). Decorin, found in many tumor beds, is a member of the small leucine-rich proteoglycan superfamily and plays important biological roles through its ability to bind other extracellular matrix proteins, certain growth factors and metal ions (Iozzo, 1999;Kresse and Scho¨nherr, 2001;Yang et al, 1999). Decorin is markedly up-regulated during quiescence in human diploid fibroblasts (Coppock et al, 1993) and vascular smooth muscle cells (Mauviel et al, 1995), but its expression is totally abrogated in most tumor cell lines tested .…”

Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling

“…Because decorin is a Zn 2ϩ metalloprotein (56), and this cation promotes the binding of decorin to fibrinogen, collagen, fibronectin (57), and myostatin (58), we performed binding experiments in the absence or presence of increasing concentrations (0 -120 M) of ZnCl 2 . Notably, we found no effect of Zn 2ϩ in modulating the binding of recombinant decorin protein core to either IGF-I or IGF-IR (not shown), indicating that this protein-protein interaction is independent of Zn 2ϩ .…”