PDBsum entry 2zpy

Cell adhesion

PDB id: 2zpy

Contents

Protein chain

295 a.a. *

Ligands

GLN-LYS-LYS-LYS-LEU-VAL-ILE-ASN-GLY

Waters ×171

* Residue conservation analysis

PDB id:

2zpy

Name:

Cell adhesion

Title:

Crystal structure of the mouse radxin ferm domain complexed with the mouse cd44 cytoplasmic peptide

Structure:

Radixin. Chain: a. Fragment: ferm domain (residues 1-310). Synonym: esp10. Engineered: yes. Cd44 antigen. Chain: b. Fragment: residues 293-312. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: rdx. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: peptide synthesis

Resolution:

2.10Å R-factor: 0.231 R-free: 0.256

Authors:

T.Mori,K.Kitano,S.Terawaki,R.Maesaki,Y.Fukami,T.Hakoshima

Key ref:

T.Mori et al. (2008). Structural basis for CD44 recognition by ERM proteins. J Biol Chem, 283, 29602-29612. PubMed id: 18753140 DOI: 10.1074/jbc.M803606200

Date:

31-Jul-08 Release date: 26-Aug-08

Protein chain

P26043  (RADI_MOUSE) -  Radixin from Mus musculus

Seq: 583 a.a.

Struc: 295 a.a.

DOI no: 10.1074/jbc.M803606200

J Biol Chem 283:29602-29612 (2008)

PubMed id: 18753140

Structural basis for CD44 recognition by ERM proteins.

T.Mori, K.Kitano, S.Terawaki, R.Maesaki, Y.Fukami, T.Hakoshima.

ABSTRACT

CD44 is an important adhesion molecule that functions as the major hyaluronan receptor which mediates cell adhesion and migration in a variety of physiological and pathological processes. Although full activity of CD44 requires binding to ERM (ezrin/radixin/moesin) proteins, the CD44 cytoplasmic region, consisting of 72 amino acid residues, lacks the Motif-1 consensus sequence for ERM binding found in intercellular adhesion molecule (ICAM)-2 and other adhesion molecules of the immunoglobulin superfamily. Ultracentrifugation sedimentation studies and circular dichroism measurements revealed an extended monomeric form of the cytoplasmic peptide in solution. The crystal structure of the radixin FERM domain complexed with a CD44 cytoplasmic peptide reveals that the KKKLVIN sequence of the peptide forms a beta strand followed by a short loop structure that binds subdomain C of the FERM domain. Like Motif-1 binding, the CD44 beta strand binds the shallow groove between strand beta5C and helix alpha1C and augments the beta sheet beta5C-beta7C from subdomain C. Two hydrophobic CD44 residues, Leu and Ile, are docked into a hydrophobic pocket with the formation of hydrogen bonds between Asn of the CD44 short loop and loop beta4C-beta5C from subdomain C. This binding mode resembles that of NEP (neutral endopeptidase 24.11) rather than ICAM-2. Our results reveal a characteristic versatility of peptide recognition by the FERM domains from ERM proteins, suggest a possible mechanism by which the CD44 tail is released from the cytoskeleton for nuclear translocation by regulated intramembrane proteolysis, and provide a structural basis for Smad1 interactions with activated CD44 bound to ERM protein.

Selected figure(s)

Figure 2.
Crystal structure of the FERM-CD44 complex. A, ribbon representations of the radixin FERM domain complexed with the CD44 cytoplasmic peptide (blue). The radixin FERM domain comprises three subdomains: A (residues 3-82 in green), B (residues 96-195 in red), and C (residues 204-297 in yellow). Linkers A-B (residues 83-95) and B-C (residues 196-203) are colored gray. B, surface electrostatic potentials of the FERM domain and a close-up view of the CD44 cytoplasmic peptide docked into the groove formed between helix α1C and strand β5C of subdomain C. The peptide is shown as a stick model (labeled with one-letter codes), and the four side chain-binding sites (S1--S4) for the bound β strand of CD44 and the deep hydrophobic pocket (P1) are labeled and indicated with yellow dashed circles. Site S4 adjoins pocket P1. C, a stick model of the CD44 cytoplasmic peptide is shown in the omit electron density map for the CD44 cytoplasmic peptide at the contour level of 1σ.

Figure 4.
Comparison of ICAM-2, NEP, and CD44 peptides bound to the FERM domain. Shown is superposition of ICAM-2 (magenta) from the FERM-ICAM-2 complex (28) and NEP (green) from the FERM-NEP complex (31) on the FERM-CD44 complex. The N-terminal extensions of ICAM-2 and CD44 or the C terminus of NEP that would be linked to the transmembrane helix in the plasmamembrane are indicated with dotted lines.

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2008, 283, 29602-29612) copyright 2008.

Figures were selected by an automated process.