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PDBsum entry 3x23
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Cell invasion
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PDB id
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3x23
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References listed in PDB file
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Key reference
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Title
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Mt1-Mmp recognition by erm proteins and its implication in cd44 shedding.
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Authors
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S.Terawaki,
K.Kitano,
M.Aoyama,
T.Mori,
T.Hakoshima.
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Ref.
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Genes Cells, 2015,
20,
847-859.
[DOI no: ]
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PubMed id
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Abstract
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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 β-β interaction with
β2A-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.
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