2JXO: Structure of the second PDZ domain of NHERF-1

Na(+)/H(+) exchanger regulatory factor (NHERF1) is a signaling adaptor protein comprising two PDZ domains and a C-terminal ezrin-binding (EB) motif. To understand the role of intramolecular interactions in regulating its binding properties, we characterized the complex between the second PDZ domain PDZ2 and the C-terminal 242-358 fragment of NHERF1 using NMR and fluorescence methods. NMR chemical shift and relaxation data implicate 11 C-terminal residues in binding and, together with a thermodynamic analysis of mutant proteins, indicate that the EB region becomes helical when bound to PDZ2. Both specific contacts between PDZ2 and EB as well as nonspecific interactions involving a 100-residue flexible linker contribute to stabilizing two structurally distinct closed conformations of NHERF1. The affinity of mutant proteins for an extrinsic ligand is inversely related to the helix-forming propensity of the EB motif. The findings provide a structural framework for understanding how autoinhibitory interactions modulated the binding properties of NHERF1.
PDB ID: 2JXODownload
MMDB ID: 68322
PDB Deposition Date: 2007/11/27
Updated in MMDB: 2008/12
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 2JXO
Label Count Molecule
Protein (1 molecule)
Ezrin-radixin-moesin-binding Phosphoprotein 50(Gene symbol: SLC9A3R1)
Molecule annotation
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Citing MMDB