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| | <StructureSection load='3c7x' size='340' side='right'caption='[[3c7x]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='3c7x' size='340' side='right'caption='[[3c7x]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3c7x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C7X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C7X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3c7x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C7X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Membrane-type_matrix_metalloproteinase-1 Membrane-type matrix metalloproteinase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.80 3.4.24.80] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c7x OCA], [http://pdbe.org/3c7x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3c7x RCSB], [http://www.ebi.ac.uk/pdbsum/3c7x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3c7x ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c7x OCA], [https://pdbe.org/3c7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c7x RCSB], [https://www.ebi.ac.uk/pdbsum/3c7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c7x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN]] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref> | + | [https://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] |
| - | *[[Molecular Playground/MMP14|Molecular Playground/MMP14]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Membrane-type matrix metalloproteinase-1]]
| + | [[Category: Bode W]] |
| - | [[Category: Bode, W]] | + | [[Category: Goettig P]] |
| - | [[Category: Goettig, P]] | + | [[Category: Itoh Y]] |
| - | [[Category: Itoh, Y]] | + | [[Category: Maskos K]] |
| - | [[Category: Maskos, K]] | + | [[Category: Tochowicz A]] |
| - | [[Category: Tochowicz, A]] | + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane protein interaction]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Metastasis]]
| + | |
| - | [[Category: Pro-mmp-2]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Timp-2]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
MMP14_HUMAN Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 A resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.
The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.,Tochowicz A, Goettig P, Evans R, Visse R, Shitomi Y, Palmisano R, Ito N, Richter K, Maskos K, Franke D, Svergun D, Nagase H, Bode W, Itoh Y J Biol Chem. 2011 Mar 4;286(9):7587-600. Epub 2010 Dec 30. PMID:21193411[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY. The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem. 2010 Nov 12;285(46):35740-9. doi: 10.1074/jbc.M110.165159. Epub 2010, Sep 13. PMID:20837484 doi:http://dx.doi.org/10.1074/jbc.M110.165159
- ↑ Gu G, Zhao D, Yin Z, Liu P. BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433. PMID:22065321 doi:10.1002/jcb.23433
- ↑ Tochowicz A, Goettig P, Evans R, Visse R, Shitomi Y, Palmisano R, Ito N, Richter K, Maskos K, Franke D, Svergun D, Nagase H, Bode W, Itoh Y. The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions. J Biol Chem. 2011 Mar 4;286(9):7587-600. Epub 2010 Dec 30. PMID:21193411 doi:10.1074/jbc.M110.178434
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