1G9O

FIRST PDZ DOMAIN OF THE HUMAN NA+/H+ EXCHANGER REGULATORY FACTOR

Summary for 1G9O

• Entry DOI: 10.2210/pdb1g9o/pdb
• Descriptor: NHE-RF (2 entities in total)
• Functional Keywords: pdz domain, nherf, complex, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 10043.50

Authors

Karthikeyan, S.,Leung, T.,Birrane, G.,Webster, G.,Ladias, J.A.A. (deposition date: 2000-11-26, release date: 2001-05-23, Last modification date: 2024-02-07)

Primary citation

Karthikeyan, S.,Leung, T.,Birrane, G.,Webster, G.,Ladias, J.A.
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, 2001

PubMed 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.

PubMed: 11352585
DOI: 10.1006/jmbi.2001.4634

Experimental method

X-RAY DIFFRACTION (1.5 Å)