Title : Structure and ligand-induced conformational change of the 39-kDa
glycoprotein from human articular chondrocytes
Abstract :
- 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