title: Procollagen C-proteinase enhancer stimulates procollagen processing by binding to the C-propeptide region only.
abstract: Bone morphogenetic protein-1 (BMP-1) and the tolloid-like metalloproteinases control several aspects of embryonic development and tissue repair. Unlike other proteinases whose activities are regulated mainly by endogenous inhibitors, regulation of BMP-1/tolloid-like proteinases relies mostly on proteins that stimulate activity. Among these, procollagen C-proteinase enhancers (PCPEs) markedly increase BMP-1/tolloid-like proteinase activity on fibrillar procollagens, in a substrate-specific manner. Here, we performed a detailed quantitative study of the binding of PCPE-1 and of its minimal active fragment (CUB1-CUB2) to three regions of the procollagen III molecule: the triple helix, the C-telopeptide, and the C-propeptide. Contrary to results described elsewhere, we found the PCPE-1-binding sites to be located exclusively in the C-propeptide region. In addition, binding and enhancing activities were found to be independent of the glycosylation state of the C-propeptide. These data exclude previously proposed mechanisms for the action of PCPEs and also suggest new mechanisms to explain how these proteins can stimulate BMP-1/tolloid-like proteinases by up to 20-fold.
authors.affiliation: Institut de Biologie et Chimie des Protéines, CNRS/Université Lyon 1 FRE3310, 69367 Lyon Cedex 7, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vadon-Le Goff
authors.forename: Daniel
authors.initials: D
authors.lastname: Kronenberg
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bourhis
authors.forename: Cécile
authors.initials: C
authors.lastname: Bijakowski
authors.forename: Nicolas
authors.initials: N
authors.lastname: Raynal
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.forename: Walter
authors.initials: W
authors.lastname: Stöcker
authors.forename: David J S
authors.initials: DJ
authors.lastname: Hulmes
authors.forename: Catherine
authors.initials: C
authors.lastname: Moali
mesh_terms: D001665:Binding Sites; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017433:Protein Structure, Secondary
chemical_list: D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C491555:PCOLCE protein, human; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1