Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction.

Stricker TP, Dumin JA, Dickeson SK, Chung L, Nagase H, Parks WC, Santoro SA
J Biol Chem. 2001 276 (31): 29375-81

PMID: 11359774 · DOI:10.1074/jbc.M102217200

Previous studies have established that ligation of keratinocyte alpha(2)beta(1) integrin by type I collagen induces expression of matrix metalloproteinase-1 (MMP-1) and that MMP-1 activity is required for the alpha(2)beta(1) integrin-dependent migration of primary keratinocytes across collagenous matrices. We now present evidence that MMP-1 binds the alpha(2)beta(1) integrin via the I domain of the alpha(2) integrin subunit. Using an enzyme-linked immunosorbent assay with purified human MMP-1 and recombinant alpha(2) integrin I domain, we showed that the alpha(2) integrin I domain specifically bound in a divalent cation-dependent manner to both the pro and active forms of MMP-1, but not to MMP-3 or MMP-13. Although both the I domain and MMP-1 bind divalent cations, MMP-1 bound, in a divalent cation-dependent manner, to alpha(2) integrin I domains containing metal ion-dependent adhesion sites motif mutations that prevent divalent cation binding to the I domain, demonstrating that the metal ion dependence is a function of MMP-1. Using a series of MMP-1-MMP-3 and MMP-1-MMP-13 chimeras, we determined that both the linker domain and the hemopexin-like domain of MMP-1 were required for optimal binding to the I domain. The alpha(2) integrin/MMP-1 interaction described here extends an emerging paradigm in matrix biology involving anchoring of proteinases to the cell surface to regulate their biological activities.

MeSH Terms (18)

Antigens, CD Binding Sites Cations, Divalent Cell Movement Cloning, Molecular Collagen Collagenases Enzyme-Linked Immunosorbent Assay Enzyme Precursors Humans Integrin alpha2 Keratinocytes Kinetics Matrix Metalloproteinase 1 Matrix Metalloproteinase 3 Matrix Metalloproteinase 13 Recombinant Fusion Proteins Recombinant Proteins

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