title: Meprin β and BMP-1 are differentially regulated by CaCl2.
abstract: The two metalloproteases meprin β and bone morphogenetic protein 1 (BMP-1) are both members of the astacin protease family. They share specificity for negatively charged residues around the scissile bond and they are expressed in overlapping compartments of the human body. One important proteolytic substrate they share is pro-collagen I. Ablation of one of the two proteases however leads to different collagen I associated phenotypes in vivo. Over the last years calcium emerged as a regulator for the proteolytic activity of both enzymes. For meprin β a reduction and for BMP-1 an increase in activity was reported under increasing calcium concentrations. Here we revisit different compartments that rely on pro-collagen I maturation and explore the crystal structure of both proteases to highlight possible calcium binding sites. With this we aim to emphasize a to date underestimated regulator that influences both proteases.
authors.affiliation: Anatomical Institute, Otto-Hahn-Platz 8, 24118 Kiel, Germany.
authors.forename: Janna
authors.initials: J
authors.lastname: Schneppenheim
authors.affiliation: Biochemical Institute, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
authors.forename: Franka
authors.initials: F
authors.lastname: Scharfenberg
authors.affiliation: Anatomical Institute, Otto-Hahn-Platz 8, 24118 Kiel, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lucius
authors.affiliation: Biochemical Institute, Otto-Hahn-Platz 9, 24118 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker-Pauly
authors.affiliation: Anatomical Institute, Otto-Hahn-Platz 8, 24118 Kiel, Germany. Electronic address: p.arnold@anat.uni-kiel.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Arnold
mesh_terms: D055395:Bone Morphogenetic Protein 1 / Q000737:chemistry* / Q000378:metabolism; D002122:Calcium Chloride / Q000737:chemistry*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D008666:Metalloendopeptidases; C053833:meprin A; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1; D002122:Calcium Chloride
keywords: BMP-1; Calcium; Meprin β; Molecular dynamics simulation