MT1‐MMP recognition by ERM proteins and its implication in CD44 shedding

DOI Web Site Web Site Web Site PubMed 58 References
  • Shin‐ichi Terawaki
    Structural Biology Laboratory Nara Institute of Science and Technology 8916‐5 Takayama Ikoma Nara 630‐0192 Japan
  • Ken Kitano
    Structural Biology Laboratory Nara Institute of Science and Technology 8916‐5 Takayama Ikoma Nara 630‐0192 Japan
  • Miki Aoyama
    Structural Biology Laboratory Nara Institute of Science and Technology 8916‐5 Takayama Ikoma Nara 630‐0192 Japan
  • Tomoyuki Mori
    Structural Biology Laboratory Nara Institute of Science and Technology 8916‐5 Takayama Ikoma Nara 630‐0192 Japan
  • Toshio Hakoshima
    Structural Biology Laboratory Nara Institute of Science and Technology 8916‐5 Takayama Ikoma Nara 630‐0192 Japan

Search this article

Description

<jats:p>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.</jats:p>

Journal

References(58)*help

See more

Related Projects

See more

Keywords

Report a problem

Back to top