PDBsum entry 2m0t

Protein binding

PDB id: 2m0t

Contents

Protein chain

117 a.a.

PDB id:

2m0t

Name:

Protein binding

Title:

Structural characterization of the extended pdz1 domain from nherf1

Structure:

Na(+)/h(+) exchange regulatory cofactor nhe-rf1. Chain: a. Fragment: pdz1 domain. Synonym: nherf-1, ezrin-radixin-moesin-binding phosphoprotein 50, ebp50, regulatory cofactor of na(+)/h(+) exchanger, sodium-hydrogen exchanger regulatory factor 1, solute carrier family 9 isoform a3 regulatory factor 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: slc9a3r1, nherf, nherf1. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

S.Bhattacharya,J.H.Ju,D.Cowburn,Z.Bu

Key ref:

S.Bhattacharya et al. (2013). Ligand-induced dynamic changes in extended PDZ domains from NHERF1. J Mol Biol, 425, 2509-2528. PubMed id: 23583913 DOI: 10.1016/j.jmb.2013.04.001

Date:

06-Nov-12 Release date: 24-Apr-13

Protein chain

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

Seq: 358 a.a.

Struc: 117 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2013.04.001

J Mol Biol 425:2509-2528 (2013)

PubMed id: 23583913

Ligand-induced dynamic changes in extended PDZ domains from NHERF1.

S.Bhattacharya, J.H.Ju, N.Orlova, J.A.Khajeh, D.Cowburn, Z.Bu.

ABSTRACT

The multi-domain scaffolding protein NHERF1 modulates the assembly and intracellular trafficking of various transmembrane receptors and ion-transport proteins. The two PDZ (postsynaptic density 95/disk large/zonula occluden 1) domains of NHERF1 possess very different ligand-binding capabilities: PDZ1 recognizes a variety of membrane proteins with high affinity, while PDZ2 only binds limited number of target proteins. Here using NMR, we have determined the structural and dynamic mechanisms that differentiate the binding affinities of the two PDZ domains, for the type 1 PDZ-binding motif (QDTRL) in the carboxyl terminus of cystic fibrosis transmembrane regulator. Similar to PDZ2, we have identified a helix-loop-helix subdomain coupled to the canonical PDZ1 domain. The extended PDZ1 domain is highly flexible with correlated backbone motions on fast and slow timescales, while the extended PDZ2 domain is relatively rigid. The malleability of the extended PDZ1 structure facilitates the transmission of conformational changes at the ligand-binding site to the remote helix-loop-helix extension. By contrast, ligand binding has only modest effects on the conformation and dynamics of the extended PDZ2 domain. The study shows that ligand-induced structural and dynamic changes coupled with sequence variation at the putative PDZ binding site dictate ligand selectivity and binding affinity of the two PDZ domains of NHERF1.