Collagen Binding Properties of the Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Hemopexin C Domain THE ECTODOMAIN OF THE 44-kDa AUTOCATALYTIC PRODUCT OF MT1-MMP INHIBITS CELL INVASION BY DISRUPTING NATIVE TYPE I COLLAGEN CLEAVAGE*

Up-regulation of the collagenolytic membrane type-1 matrix metalloproteinase (MT1-MMP) leads to increased MMP2 (gelatinase A) activation and MT1-MMP autoly-sis. The autocatalytic degradation product is a cell sur-face 44-kDa fragment of MT1-MMP (Gly285–Val582) in which the ectodomain consists of only the linker, he-mopexin C domain and the stalk segment found before the transmembrane sequence. In the collagenases, he-mopexin C domain exosites bind native collagen, which is required for triple helicase activity during collagen cleavage. Here we investigated the collagen binding properties and the role of the hemopexin C domain of MT1-MMP and of the 44-kDa MT1-MMP ectodomain in collagenolysis. Recombinant proteins, MT1-LCD (Gly285–Cys508), consisting of the linker and the he