Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan.
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 beta-sheet on the inside interwoven with loops containing short segments of beta-strands, 3(10) 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.
Scott
Paul G
PG
Department of Biochemistry and Alberta Synchrotron Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
McEwan
Paul A
PA
Dodd
Carole M
CM
Bergmann
Ernst M
EM
Bishop
Paul N
PN
Bella
Jordi
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D058575:Decorin; D019281:Dimerization; D016326:Extracellular Matrix Proteins; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D011509:Proteoglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008024:Ligands; D011509:Proteoglycans; D011994:Recombinant Proteins