期刊
GENES TO CELLS
卷 20, 期 10, 页码 847-859出版社
WILEY
DOI: 10.1111/gtc.12276
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Uehara Memorial Foundation, Japan
- Grants-in-Aid for Scientific Research [26251006, 22121002, 25840017, 25440024] Funding Source: KAKEN
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 beta 2A-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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