| Structural highlights
3x23 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1gc7, 1j19, 2yvc, 2ems, 2emt, 2d2q, 1gc6, 2d10, 2d11, 1isn, 2zpy |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[RADI_MOUSE] Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane. [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]
Publication Abstract from PubMed
Membrane type 1-matrix metalloproteinase (MT1-MMP) is a key enzyme involved in tumor cell invasion by shedding their cell-surface receptor CD44 anchored with F-actin through ezrin/radixin/moesin (ERM) proteins. We found the cytoplasmic tail of MT1-MMP directly binds the FERM domain of radixin, suggesting F-actin-based recruitment of MT1-MMP to CD44 for invasion. Our crystal structure shows that the central region of the MT1-MMP cytoplasmic tail binds subdomain A of the FERM domain, and makes an antiparallel beta-beta interaction with beta2A-strand. This binding mode is distinct from the previously determined binding mode of CD44 to subdomain C. We showed that radixin simultaneously binds both MT1-MMP and CD44, indicating ERM protein-mediated colocalization of MT1-MMP and its substrate CD44 and anchoring to F-actin. Our study implies that ERM proteins contribute toward accelerated CD44 shedding by MT1-MMP through ERM protein-mediated interactions between their cytoplasmic tails.
MT1-MMP recognition by ERM proteins and its implication in CD44 shedding.,Terawaki S, Kitano K, Aoyama M, Mori T, Hakoshima T Genes Cells. 2015 Oct;20(10):847-59. doi: 10.1111/gtc.12276. Epub 2015 Aug 20. PMID:26289026[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Terawaki S, Kitano K, Aoyama M, Mori T, Hakoshima T. MT1-MMP recognition by ERM proteins and its implication in CD44 shedding. Genes Cells. 2015 Oct;20(10):847-59. doi: 10.1111/gtc.12276. Epub 2015 Aug 20. PMID:26289026 doi:http://dx.doi.org/10.1111/gtc.12276
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