PDBsum entry 3x23

Cell invasion

PDB id: 3x23

Contents

Protein chains

299 a.a.

11 a.a.

Waters ×179

PDB id:

3x23

Name:

Cell invasion

Title:

Radixin complex

Structure:

Radixin. Chain: a. Fragment: ferm domain, unp reisudes 1-310. Synonym: esp10. Engineered: yes. Peptide from matrix metalloproteinase-14. Chain: b. Fragment: cytoplasmic tail, unp residues 563-582. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: rdx. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Human.

Resolution:

2.40Å R-factor: 0.193 R-free: 0.238

Authors:

S.Terawaki,K.Kitano,M.Aoyama,T.Mori,T.Hakoshima

Key ref:

S.Terawaki et al. (2015). MT1-MMP recognition by ERM proteins and its implication in CD44 shedding. Genes Cells, 20, 847-859. PubMed id: 26289026 DOI: 10.1111/gtc.12276

Date:

09-Dec-14 Release date: 21-Oct-15

Protein chain

P26043  (RADI_MOUSE) -  Radixin from Mus musculus

Seq: 583 a.a.

Struc: 299 a.a.

Protein chain

P50281  (MMP14_HUMAN) -  Matrix metalloproteinase-14 from Homo sapiens

Seq: 582 a.a.

Struc: 11 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.3.4.24.80 - membrane-type matrix metalloproteinase-1.
• Cofactor: Zn(2+)

DOI no: 10.1111/gtc.12276

Genes Cells 20:847-859 (2015)

PubMed id: 26289026

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

S.Terawaki, K.Kitano, M.Aoyama, T.Mori, T.Hakoshima.

ABSTRACT

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.