Type I Collagen Stabilization of Matrix Metalloproteinase-2.

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.