title: The second dimer interface of MT1-MMP, the transmembrane domain, is essential for ProMMP-2 activation on the cell surface.
abstract: Activation of proMMP-2 and cell surface collagenolysis are important activities of membrane-type 1 matrix metalloproteinase (MT1-MMP) to promote cell migration in tissue, and these activities are regulated by homodimerization of MT1-MMP on the cell surface. In this study, we have identified the transmembrane domain as a second dimer interface of MT1-MMP in addition to the previously identified hemopexin domain. Our analyses indicate that these two modes of dimerization have different roles; transmembrane-dependent dimerization is critical for proMMP-2 activation, whereas hemopexin-dependent dimerization is important for degradation of collagen on the cell surface. Our finding provides new insight into the potential molecular arrangement of MT1-MMP contributing to its function on the cell surface.
authors.affiliation: Department of Matrix Biology, Imperial College London, Hammersmith, London W6 8LH, UK. y.itoh@imperial.ac.uk
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Itoh
authors.forename: Noriko
authors.initials: N
authors.lastname: Ito
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D002522:Chlorocebus aethiops; D003094:Collagen / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012995:Solubility
chemical_list: D011498:Protein Precursors; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14