3c7x: Difference between revisions
No edit summary |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Hemopexin-like domain of matrix metalloproteinase 14== | |||
<StructureSection load='3c7x' size='340' side='right'caption='[[3c7x]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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'>[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> | |||
== Function == | |||
[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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c7/3c7x_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3c7x ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:21193411</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3c7x" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Matrix metalloproteinase|Matrix metalloproteinase]] | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bode | [[Category: Bode W]] | ||
[[Category: Goettig | [[Category: Goettig P]] | ||
[[Category: Itoh | [[Category: Itoh Y]] | ||
[[Category: Maskos | [[Category: Maskos K]] | ||
[[Category: Tochowicz | [[Category: Tochowicz A]] | ||
Latest revision as of 12:44, 6 November 2024
Hemopexin-like domain of matrix metalloproteinase 14Hemopexin-like domain of matrix metalloproteinase 14
Structural highlights
FunctionMMP14_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 PubMedHomodimerization 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 AlsoReferences
|
| ||||||||||||||||||