PDBsum entry 1g9o

Signaling protein

PDB id: 1g9o

Contents

Protein chain

91 a.a. *

Waters ×144

* Residue conservation analysis

PDB id:

1g9o

Name:

Signaling protein

Title:

First pdz domain of the human na+/h+ exchanger regulatory factor

Structure:

Nhe-rf. Chain: a. Fragment: pdz1 domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nherf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å R-factor: 0.181 R-free: 0.201

Authors:

S.Karthikeyan,T.Leung,G.Birrane,G.Webster,J.A.A.Ladias

Key ref:

S.Karthikeyan et al. (2001). Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-terminal leucine recognition by class I PDZ domains. J Mol Biol, 308, 963-973. PubMed id: 11352585 DOI: 10.1006/jmbi.2001.4634

Date:

26-Nov-00 Release date: 23-May-01

Protein chain

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

Seq: 358 a.a.

Struc: 91 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1006/jmbi.2001.4634

J Mol Biol 308:963-973 (2001)

PubMed id: 11352585

Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-terminal leucine recognition by class I PDZ domains.

S.Karthikeyan, T.Leung, G.Birrane, G.Webster, J.A.Ladias.

ABSTRACT

The Na(+)/H(+) exchanger regulatory factor (NHERF; also known as EBP50) contains two PDZ domains that mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. The NHERF PDZ1 domain interacts specifically with the motifs DSLL, DSFL, and DTRL present at the carboxyl termini of the beta(2) adrenergic receptor (beta(2)AR), the platelet-derived growth factor receptor (PDGFR), and the cystic fibrosis transmembrane conductance regulator (CFTR), respectively, and plays a central role in the physiological regulation of these proteins. The crystal structure of the human NHERF PDZ1 has been determined at 1.5 A resolution using multiwavelength anomalous diffraction phasing. The overall structure is similar to known PDZ structures, with notable differences in the NHERF PDZ1 carboxylate-binding loop that contains the GYGF motif, and the variable loop between the beta2 and beta3 strands. In the crystalline state, the carboxyl-terminal sequence DEQL of PDZ1 occupies the peptide-binding pocket of a neighboring PDZ1 molecule related by 2-fold crystallographic symmetry. This structure reveals the molecular mechanism of carboxyl-terminal leucine recognition by class I PDZ domains, and provides insights into the specificity of NHERF interaction with the carboxyl termini of several membrane receptors and ion channels, including the beta(2)AR, PDGFR, and CFTR.

Selected figure(s)

Figure 7.
Figure 7. Two-dimensional schematic representation of the contacts observed in the NHERF PDZ1 binding pocket. PDZ1 residues (orange) making hydrogen bonds and hydrophobic contacts with the peptide ligand (purple) are shown in ball-and-stick representation. Carbon atoms are shown in white, oxygen atoms in red, and nitrogen atoms in blue. Water molecules are shown as green spheres. Hydrogen bonds are depicted as broken lines and numbers indicate distances in Å. Val76 involved in hydrophobic interaction with the C^d2 atom of Leu0 is shown as an arc with radial spokes. The Figure was generated using the program LIGPLOT[49].

Figure 8.
Figure 8. Carboxyl-terminal leucine and valine recognition by PDZ domains. Surface representation of the hydrophobic pockets of (a) human NHERF PDZ1 and (b) rat PSD-95 PDZ3 bound to carboxyl-terminal leucine and valine residues, respectively. The limits of the hydrophobic cavities are denoted with jagged edges. The Figure was made with the program GRASP[50].

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 308, 963-973) copyright 2001.

Figures were selected by an automated process.