title: Type I collagen stabilization of matrix metalloproteinase-2.
abstract: The activity of matrix metalloproteinase-2 (MMP-2) is regulated stringently on the posttranslational level. MMP-2 efficiently undergoes autolysis into inactive polypeptides in vitro, prompting the hypothesis that MMP-2 autolysis may function as an alternative mechanism for posttranslational control of MMP-2 in vivo. Moreover, MMP-2 binds to intact type I collagen fibrils; however, the functional consequences of this interaction have not been fully elucidated. To test the hypothesis that MMP-2 binding to type I collagen functions as a positive regulator of MMP-2 proteolytic potential, the effect of type I collagen on MMP-2 activity, inhibition by tissue inhibitor of metalloproteinase-2 (TIMP-2), and enzyme stability was examined. Here, we report that purified MMP-2 binds but does not cleave intact type I collagen. The presence of type I collagen affects neither enzymatic activity against a quenched fluorescent peptide substrate nor the kinetics of inhibition by TIMP-2. However, MMP-2 is stabilized from autolysis in the presence of type I collagen, but not by elastin, fibrinogen, or laminin. These data provide biochemical evidence that MMP-2 exosite interactions with type I collagen may function in the posttranslational control of MMP-2 activity by reducing the rate of autolytic inactivation.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Ellerbroek
authors.forename: Y I
authors.initials: YI
authors.lastname: Wu
authors.forename: M S
authors.initials: MS
authors.lastname: Stack
mesh_terms: D001329:Autolysis; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D004795:Enzyme Stability / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020778:Matrix Metalloproteinase 2