Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes.
The 39-kDa human cartilage glycoprotein (HCGP39), a member of a novel family of chitinase-like lectins (Chilectins), is overexpressed in articular chondrocytes and certain cancers. Proposed functions of this protein include a role in connective tissue remodeling and defense against pathogens. Similar to other Chi-lectins, HCGP39 promotes the growth of connective tissue cells. The ability of HCGP39 to activate cytoplasmic signaling pathways suggests the presence of a ligand for this protein at the cell surface. There is currently no information regarding the identity of any physiological or pathological ligands of the Chi-lectins or the nature of the protein-ligand interaction. Here, we show that HCGP39 is able to bind chitooligosaccharides with micromolar affinity. Crystal structures of the native protein and a complex with GlcNAc8 show that the ligand is bound in identical fashion to family 18 chitinases. However, unlike the chitinases, binding of the oligosaccharide ligand to HCGP39 induces a large conformational change. Thus, HCGP39 could be a lectin that binds chitin-like oligosaccharide ligands and possibly plays a role in innate responses to chitinous pathogens, such as fungi and nematodes.
Houston
Douglas R
DR
Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Recklies
Anneliese D
AD
Krupa
Joanne C
JC
van Aalten
Daan M F
DM
D054392:Adipokines; D000071451:Chitinase-3-Like Protein 1; D019902:Chondrocytes / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004583:Electrons; D006023:Glycoproteins; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D008024:Ligands; D009844:Oligosaccharides