Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B.
The degradative actions of cathepsins L and B on human articular-cartilage proteoglycan aggregates were examined. Cathepsin L was found to be much more extensive than cathepsin B in degrading proteoglycan aggregates. It released products with size similar to that of single chondroitin sulphate chains, and a series of degraded link-protein fragments in the digestion mixtures. These proteolytically modified link-protein components (Mr 25,000 and 33,000) have similar Mr values to those of fragments observed in adult human cartilage. In contrast, cathepsin B exhibited a much more limited degradation on both proteoglycan subunits and link-protein components. Both cathepsins L and B generate multiple but distinct cleavage sites on human link proteins, and the hydrolysed bonds have been identified in the region between residues 18 and 29. Protein sequencing analysis of these modified link-protein components also provided evidence for the location of a second N-linked glycosylation site at residue 41 in human link proteins, in addition to that previously described at residue 6 on a proportion of the link proteins. Furthermore, it allows us to report the sequence of human link protein up to residue 65.
Nguyen
Q
Q
Joint Diseases Laboratory, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.
Mort
J S
JS
Roughley
P J
PJ
D000595:Amino Acid Sequence; D002358:Cartilage, Articular / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D016326:Extracellular Matrix Proteins; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis; D011509:Proteoglycans / Q000378:metabolism*; D013379:Substrate Specificity; D000099249:Proteoglycan Link Protein
D002401:Cathepsin B; D056668:Cathepsin L; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D016326:Extracellular Matrix Proteins; D011506:Proteins; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein; C534281:CTSL protein, human