PDBsum entry 2d10

Cell adhesion

PDB id: 2d10

Contents

Protein chains

295 a.a. *

20 a.a. *

Waters ×617

* Residue conservation analysis

PDB id:

2d10

Name:

Cell adhesion

Title:

Crystal structure of the radixin ferm domain complexed with the nherf- 1 c-terminal tail peptide

Structure:

Radixin. Chain: a, b, c, d. Fragment: ferm domain (residues 3-312). Synonym: esp10. Engineered: yes. Ezrin-radixin-moesin binding phosphoprotein 50. Chain: e, f, g, h. Fragment: residues 331-358. Synonym: sodium-hydrogen exchanger regulatory factor 1, ebp50, na+,

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.230 R-free: 0.268

Authors:

S.Terawaki,R.Maesaki,T.Hakoshima

Key ref:

S.Terawaki et al. (2006). Structural basis for NHERF recognition by ERM proteins. Structure, 14, 777-789. PubMed id: 16615918 DOI: 10.1016/j.str.2006.01.015

Date:

11-Aug-05 Release date: 18-Jul-06

Protein chains

P26043  (RADI_MOUSE) -  Radixin from Mus musculus

Seq: 583 a.a.

Struc: 295 a.a.

Protein chains

O14745  (NHRF1_HUMAN) -  Na(+)/H(+) exchange regulatory cofactor NHE-RF1 from Homo sapiens

Seq: 358 a.a.

Struc: 20 a.a.

DOI no: 10.1016/j.str.2006.01.015

Structure 14:777-789 (2006)

PubMed id: 16615918

Structural basis for NHERF recognition by ERM proteins.

S.Terawaki, R.Maesaki, T.Hakoshima.

ABSTRACT

The Na+/H+ exchanger regulatory factor (NHERF) is a key adaptor protein involved in the anchoring of ion channels and receptors to the actin cytoskeleton through binding to ERM (ezrin/radixin/moesin) proteins. NHERF binds the FERM domain of ERM proteins, although NHERF has no signature Motif-1 sequence for FERM binding found in adhesion molecules. The crystal structures of the radixin FERM domain complexed with the NHERF-1 and NHERF-2 C-terminal peptides revealed a peptide binding site of the FERM domain specific for the 13 residue motif MDWxxxxx(L/I)Fxx(L/F) (Motif-2), which is distinct from Motif-1. This Motif-2 forms an amphipathic alpha helix for hydrophobic docking to subdomain C of the FERM domain. This docking causes induced-fit conformational changes in subdomain C and affects binding to adhesion molecule peptides, while the two binding sites are not overlapped. Our studies provide structural paradigms for versatile ERM linkages between membrane proteins and the cytoskeleton.

Selected figure(s)

Figure 2.
Figure 2. The FERM-NHERF Interactions
(A) Front (left) and side (right) views of surface electrostatic potentials of the radixin FERM domain. The front view is viewed from the same direction as in Figure 1A. Positive (blue, +14 kT/e) and negative (red, −14 kT/e) potentials are mapped on the van der Waals surfaces. The four crystallographic-independent NHERF-1 peptides are shown in tube models (cyan). A side view of the FERM domain is shown without the NHERF-1 peptide to show two hydrophobic pockets for the Trp348 and Phe355 side chains from the NHERF peptide.
(B) A close-up view of the amphipathic helix of the NHERF-1 peptide (cyan) docked to the groove formed by the β sandwich of subdomain C (yellow). Hydrogen bonds are shown with dotted lines. The C-terminal carboxyl group of Leu358 is labeled with CPX.
(C) Schematic diagram of the interaction between the NHERF-1 peptide (residues 339–358, cyan main chain bonds) and the FERM domain (brown main chain bonds) with atom colors: black, C; blue, N; red, O; yellow, S. Polar contacts are shown with red, dashed lines, and hydrophobic contacts are indicated by arcs with radiating spokes. A list of all residues involved in binding either peptide together with their distances is given in Table S2.
(D) A close-up view of the superimposed C-terminal region of NHERF-1 (blue) and NHERF-2 (yellow) peptides bound to the FERM domains. Leu354 and the C-terminal end residue of NHERF-1, Leu358, are replaced with Ile333 and Phe337 in NHERF-2, respectively. These residues interact with residues from the FERM domains drawn in cyan (NHERF-1 bound form) and gray (NHERF-2 bound form).

Figure 4.
Figure 4. Multiple Binding Modes Found in the FERM Domain of ERM Proteins
(A) The radixin FERM domain (gray) complexed with IP3 (Hamada et al., 2000), which is shown as a ball-and-stick model. Italic labels indicate subdomains A, B, and C.
(B) The radixin FERM domain complexed with the ICAM-2 cytoplasmic peptide (magenta) (Hamada et al., 2003).
(C) The radixin FERM domain complexed with the NHERF-1 peptide (blue; this work).
(D) The moesin FERM domain complexed the C-tail domain (dark brown) (Pearson et al., 2000).
(E) The C-tail domain (brown) is superimposed with the NHERF-1 peptide (blue) bound to the radixin FERM domain (gray).
(F) Comparison of the C-terminal helix of the NHERF-1 peptide (light blue) bound to the radixin FERM domain and helix D of the moesin C-tail domain (brown).

The above figures are reprinted by permission from Cell Press: Structure (2006, 14, 777-789) copyright 2006.

Figures were selected by an automated process.