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Crystal structure of human cartilage gp39 (HC-gp39)
Structural highlights
Disease[CH3L1_HUMAN] A genetic variation in CHI3L1 is associated with susceptibility to asthma-related traits type 7 (ASRT7) [MIM:611960]. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing and dyspnea, bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test, serum IgE levels, atopy, and atopic dermatitis. Function[CH3L1_HUMAN] Carbohydrate-binding lectin with a preference for chitin. May play a role in defense against pathogens, or in tissue remodeling. May play an important role in the capacity of cells to respond to and cope with changes in their environment.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe human cartilage glycoprotein-39 (HCgp-39 or YKL40) is expressed by synovial cells and macrophages during inflammation. Its precise physiological role is unknown. However, it has been proposed that HCgp-39 acts as an autoantigen in rheumatoid arthritis, and high expression levels have been associated with cancer development. HCgp-39 shares high sequence homology with family 18 chitinases, and although it binds to chitin it lacks enzymatic activity. The crystal structure of HCgp-39 shows that the protein displays a (beta/alpha)8-barrel fold with an insertion of an alpha + beta domain. A 43-A long carbohydrate-binding cleft is present at the C-terminal side of the beta-strands in the (beta/alpha)8 barrel. Binding of chitin fragments of different lengths identified nine sugar-binding subsites in the groove. Protein-carbohydrate interactions are mainly mediated by stacking of side chains of aromatic amino acid residues. Surprisingly, the specificity of chitin binding to HCgp-39 depends on the length of the oligosaccharide. Although chitin disaccharides tend to occupy the distal subsites, longer chains bind preferably to the central subsites in the groove. Despite the absence of enzymatic activity, long chitin fragments are distorted upon binding, with the GlcNAc at subsite -1 in a boat conformation, similar to what has been observed in chitinases. The presence of chitin in the human body has never been documented so far. However, the binding features observed in the complex structures suggest that either chitin or a closely related oligosaccharide could act as the physiological ligand for HCgp-39. Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39.,Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW J Biol Chem. 2003 Sep 26;278(39):37753-60. Epub 2003 Jul 8. PMID:12851408[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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