title: Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V.
abstract: Processing of fibrillar collagens is required to generate collagen monomers able to self-assemble into elongated and cylindrical collagen fibrils. ADAMTS-2 belongs to the "A disintegrin and metalloproteinase with thrombospondin type 1 motifs" (ADAMTS) family. It is responsible for most of the processing of the aminopropeptide of type I procollagen in the skin, and it also cleaves type II and type III procollagens. ADAMTS are complex secreted enzymes that are implicated in various physiological and pathological processes. Despite accumulating evidence indicating that their activity is regulated by ancillary domains, additional information is required for a better understanding of the specific function of each domain. We have generated 17 different recombinant forms of bovine ADAMTS-2 and characterized their processing, activity, and cleavage specificity. The results indicated the following: (i) activation of the ADAMTS-2 zymogen involves several cleavages, by proprotein convertases and C-terminal processing, and generates at least seven distinct processed forms; (ii) the C-terminal domain negatively regulates enzyme activity, whereas two thrombospondin type 1 repeats are enhancer regulators; (iii) the 104-kDa form displays the highest aminoprocollagen peptidase activity on procollagen type I; (iv) ADAMTS-2 processes the aminopropeptide of alpha1 type V procollagen homotrimer at the end of the variable domain; and (v) the cleaved sequence (PA) is different from the previously described sites ((P/A)Q) for ADAMTS-2, redefining its cleavage specificity. This finding and the existence of multiple processed forms of ADAMTS-2 strongly suggest that ADAMTS-2 may be involved in function(s) other than processing of fibrillar procollagen types I-III.
authors.affiliation: Laboratory of Connective Tissues Biology, Center of Biomedical Integrative Genoproteomics, University of Liège, B-4000 SartTilman, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
authors.forename: Isabel
authors.initials: I
authors.lastname: Vandenberghe
authors.forename: Johanne
authors.initials: J
authors.lastname: Dubail
authors.forename: Frederic
authors.initials: F
authors.lastname: Kesteloot
authors.forename: Jozef
authors.initials: J
authors.lastname: Van Beeumen
authors.forename: Alain
authors.initials: A
authors.lastname: Beschin
authors.forename: Lea
authors.initials: L
authors.lastname: Brys
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lapière
authors.forename: Betty
authors.initials: B
authors.lastname: Nusgens
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry*; D000071096:ADAMTS Proteins; D000071121:ADAMTS4 Protein; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D002384:Catalysis; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003094:Collagen / Q000737:chemistry; D024042:Collagen Type I / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry*; D024061:Collagen Type III / Q000737:chemistry*; D024062:Collagen Type V / Q000737:chemistry*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D010455:Peptides / Q000737:chemistry; D011348:Procollagen N-Endopeptidase / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013696:Temperature; D014162:Transfection
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D024062:Collagen Type V; D010455:Peptides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D003094:Collagen; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C000609307:ADAMTS2 protein, human; C000609308:Adamts2 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein