Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan

Abstract

Decorin is a ubiquitous extracellular matrix proteoglycan with a variety of important biological functions that are mediated by its interactions with extracellular matrix proteins, cytokines, and cell surface receptors. Decorin is the prototype of the family of small leucine-rich repeat proteoglycans and proteins (SLRPs), characterized by a protein core composed of leucine-rich repeats (LRRs), flanked by two cysteine-rich regions. We report here the crystal structure of the dimeric protein core of decorin, the best characterized member of the SLRP family. Each monomer adopts the curved solenoid fold characteristic of LRR domains, with a parallel ␤-sheet on the inside interwoven with loops containing short segments of ␤-strands, 310 helices, and polyproline II helices on the outside. Two main features are unique to this structure. First, decorin dimerizes through the concave surfaces of the LRR domains, which have been implicated previously in protein-ligand interactions. The amount of surface buried in this dimer rivals the buried surfaces of some of the highest-affinity macromolecular complexes reported to date. Second, the C-terminal region adopts an unusual capping motif that involves a laterally extended LRR and a disulfide bond. This motif seems to be unique to SLRPs and has not been observed in any other LRR protein structure to date. Possible implications of these features for decorin ligand binding and SLRP function are discussed.

Microfibrillar structure of type I collagen in situ

“…The torsion on the supertwist would be converted into a force that is transmitted three-dimensionally through the crosslinked molecular array to neighboring collagen molecules in neighboring microfibrillar cords. These crosslinks are found at both the (axially contracted) N-telopeptide and the (folded) C-terminal telopeptide, which is crosslinked with the neighboring 1D staggered C-and Nterminal collagen segments, respectively (7,25) (Figs. 2C, 3D, and 4).…”

“…These segments contain two of the several sites that have been implicated for decorin binding, at 0.8D and 0.6D (and 1.6D) of collagens' molecular length (30, 31) (also equivalent to 0.8D and 0.6D within the 1D staggered packing system). If collagen molecules on the surface of the fibril are similarly structured, then these locations are clearly suited to accommodate the large decorin protein core, whether in monomeric (32) or dimeric (25,33) form, although this finding certainly does not preclude the viability of other proposed binding sites along the collagen fibril's surface. The significance of the 0.6D and 0.8D sites revealed by the electron density map and model presented here is that each could provide a ''niche'' (shallow hole) in the growing fibril surface that would provide a larger proteinto-protein contact area, and therefore the potentially stronger association between decorin and collagen, than at other possible (and flatter) decorin binding sites, while still allowing decorin to ''stick out'' of the fibril surface sufficiently to be effective in regulating fibril diameter.…”

“…The coordinates for the monomeric decorin model (39), the recombinant decorin dimer [Protein Data Bank (PDB) ID codes 1XKU, 1XEC, and 1XCD] (25), and fibroblast collagenase model (PDB ID code 1FBL) (40) were used to perform initial studies of collagen-decorin and collagen-collagenase interactions within the context of the structure presented here. All model structures were viewed by using SPOCK (http:͞͞quorum.…”

The Decorin Sequence SYIRIADTNIT Binds Collagen Type I

“…The decorin core protein is composed of 12 tandem leucine-rich repeats (LRRs), each containing an average of 24 amino acid residues. The decorin threedimensional structure, resolved by x-ray crystallography, reveals an arch-shaped molecule with LRRs composed of parallel ␤-sheets on the concave surface and short ␤-strands, 3 10 helices, and polyproline II helices on the convex face (10). Close to the N terminus, decorin is substituted with a single chondroitin or dermatan sulfate chain.…”

Decorin, a Novel Player in the Insulin-like Growth Factor System

“…In addition, they carry at least a single glycosaminoglycan chain. Recently, a crystal structure for bovine decorin has been published (1) that together with earlier x-ray scattering data (2) suggests that decorin is a dimeric protein with 12 leucine-rich repeat motifs that include the N-and C-terminal cysteine-rich regions. This numbering of leucine-rich repeats is subsequently used in this report.…”