PDBsum entry 1gc7

Cell adhesion

PDB id: 1gc7

Contents

Protein chain

297 a.a. *

* Residue conservation analysis

PDB id:

1gc7

Name:

Cell adhesion

Title:

Crystal structure of the radixin ferm domain

Structure:

Radixin. Chain: a. Fragment: ferm domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.215 R-free: 0.255

Authors:

K.Hamada,T.Shimizu,T.Matsui,S.Tsukita,S.Tsukita,T.Hakoshima

Key ref:

K.Hamada et al. (2000). Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. EMBO J, 19, 4449-4462. PubMed id: 10970839 DOI: 10.1093/emboj/19.17.4449

Date:

21-Jul-00 Release date: 20-Sep-00

Protein chain

P26043  (RADI_MOUSE) -  Radixin from Mus musculus

Seq: 583 a.a.

Struc: 297 a.a.

DOI no: 10.1093/emboj/19.17.4449

EMBO J 19:4449-4462 (2000)

PubMed id: 10970839

Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.

K.Hamada, T.Shimizu, T.Matsui, S.Tsukita, T.Hakoshima.

ABSTRACT

Radixin is a member of the ezrin/radixin/moesin (ERM) family of proteins, which play a role in the formation of the membrane-associated cytoskeleton by linking actin filaments and adhesion proteins. This cross-linking activity is regulated by phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) in the downstream of the small G protein Rho. The X-ray crystal structures of the radixin FERM domain, which is responsible for membrane binding, and its complex with inositol-(1,4, 5)-trisphosphate (IP3) have been determined. The domain consists of three subdomains featuring a ubiquitin-like fold, a four-helix bundle and a phosphotyrosine-binding-like domain, respectively. These subdomains are organized by intimate interdomain interactions to form characteristic grooves and clefts. One such groove is negatively charged and so is thought to interact with basic juxta-membrane regions of adhesion proteins. IP3 binds a basic cleft that is distinct from those of pleckstrin homology domains and is located on a positively charged flat molecular surface, suggesting an electrostatic mechanism of plasma membrane targeting. Based on the structural changes associated with IP3 binding, a possible unmasking mechanism of ERM proteins by PIP2 is proposed.

Selected figure(s)

Figure 4.
Figure 4 Subdomain structures of the radixin FERM domain. The color codes used are light green for radixin subdomains, light blue for ubiquitin, yellow for acyl-coenzyme A binding protein, red for the PTB domain and orange for the PH domain. (A) Superimposition of radixin subdomain A on ubiquitin (PDB code 1UBI, blue). (B) Superimposition of radixin subdomain B on E.coli acyl-coenzyme A binding protein (yellow, 1ACA). (C) Superimposition of radixin subdomain C on the IRS-1 PTB domain (1QQG, red). (D) Superimposition of radixin subdomain C on the PH domain (1PLS, orange). (E) Comparison of the IP3-binding sites found in the radixin FERM domain (left), the phospholipase C 1 PH domain (middle) and the -spectrin PH domain (right). Two loops forming the binding site of each PH domain are colored in blue. The binding site of the radixin FERM domain is located at the basic cleft between subdomains A (a ubiquitin-like fold in light green) and C (a PTB-like fold in light blue) (see text). The N-terminal half of helix 1C of subdomain C and the protruding loop between strands 3A and 5A of subdomain A form the IP3-binding site of the radixin FERM domain and are colored in blue.

Figure 5.
Figure 5 Molecular surface properties of the radixin FERM domain. (A) Surface electrostatic potentials of the radixin FERM domain viewed from the same direction as in Figure 2A. Positive (blue) and negative (red) potentials are mapped on the van der Waals surfaces. The IP3 molecule found in the complex crystal is shown in a stick model. (B) Surface electrostatic potentials viewed along the arrow b in (A) to show the basic cleft between subdomains A and C. The IP3 molecule found in the complex crystal is shown in a stick model. (C) Surface electrostatic potentials viewed along arrow c in (A) to show the acidic groove between subdomains B and C. (D) A backside view of surface electrostatic potentials seen in (A). The IP3 molecule found in the complex crystal is shown in a stick model. (E) Conserved residues of the radixin FERM domain mapped on the molecular surfaces. A front view of the radixin FERM domain depicted as a colored molecular surface using a gradient; orange indicates conserved identical residues and white non-conserved residues, while lighter shades of orange indicate semi-invariant residues. A view from the same direction as in (A) and Figure 2A. (F) Back view of conserved residues of the radixin FERM domain. (G) Front view of hydrophobic residues of the radixin FERM domain mapped on the molecular surfaces. (H) Back view of hydrophobic residues of the radixin FERM domain.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 4449-4462) copyright 2000.

Figures were selected by an automated process.