title: Bone morphogenetic protein-1 (BMP-1) mediates C-terminal processing of procollagen V homotrimer.
abstract: The processing of the fibrillar procollagen precursors to mature collagens is an essential requirement for fibril formation. The enzymes involved in these events are known as the procollagen N and C proteinases. The latter, which cleaves the C-propeptides of the fibrillar procollagens I-III, is identical to the previously described bone morphogenetic protein-1 (BMP-1). Surprisingly, unlike the other fibrillar collagens, the processing of the C-propeptide domain of the procollagen V homotrimer was found to be mediated by furin rather than BMP-1. However, the presence of putative BMP-1 cleavage sites in the alpha1(V) C-propeptide sequence prompted us to reconsider the procollagen V C-propeptide cleavage by BMP-1. Using a recombinant system to produce substantial amounts of the proalpha1(V) homotrimer, we have previously shown that the C-propeptide is spontaneously released in the culture medium. The trimeric C-propeptide fragment, resulting from the furin cleavage, still encompassed the predicted BMP-1 cleavage sites. It was purified and tested as a substrate for BMP-1. In parallel, the release of the C-propeptide in the culture medium was inhibited by the addition of a specific furin inhibitor, allowing the re-examination of BMP-1 activity on the intact molecule. We showed that BMP-1 does cleave both substrates at one of the two predicted C-proteinase cleavage sites. Our results favor a role for PCP/BMP-1 in physiological C-terminal processing of procollagen V and imply a general mechanism for fibrillar collagen C-terminal processing.
authors.affiliation: Tel-Aviv University Sackler Faculty of Medicine, Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Kessler
authors.forename: A
authors.initials: A
authors.lastname: Fichard
authors.forename: H
authors.initials: H
authors.lastname: Chanut-Delalande
authors.forename: M
authors.initials: M
authors.lastname: Brusel
authors.forename: F
authors.initials: F
authors.lastname: Ruggiero
mesh_terms: D000595:Amino Acid Sequence; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D006868:Hydrolysis; D008666:Metalloendopeptidases / Q000502:physiology*; D011347:Procollagen / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D003470:Culture Media; D011347:Procollagen; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1