2KRG

Solution Structure of human sodium/ hydrogen exchange regulatory factor 1(150-358)


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A conformational switch in the scaffolding protein NHERF1 controls autoinhibition and complex formation.

Bhattacharya, S.Dai, Z.Li, J.Baxter, S.Callaway, D.J.E.Cowburn, D.Bu, Z.

(2010) J Biol Chem 285: 9981-9994

  • DOI: https://doi.org/10.1074/jbc.M109.074005
  • Primary Citation of Related Structures:  
    2KRG

  • PubMed Abstract: 

    The mammalian Na(+)/H(+) exchange regulatory factor 1 (NHERF1) is a multidomain scaffolding protein essential for regulating the intracellular trafficking and macromolecular assembly of transmembrane ion channels and receptors. NHERF1 consists of tandem PDZ-1, PDZ-2 domains that interact with the cytoplasmic domains of membrane proteins and a C-terminal (CT) domain that binds the membrane-cytoskeleton linker protein ezrin. NHERF1 is held in an autoinhibited state through intramolecular interactions between PDZ2 and the CT domain that also includes a C-terminal PDZ-binding motif (-SNL). We have determined the structures of the isolated and tandem PDZ2CT domains by high resolution NMR using small angle x-ray scattering as constraints. The PDZ2CT structure shows weak intramolecular interactions between the largely disordered CT domain and the PDZ ligand binding site. The structure reveals a novel helix-turn-helix subdomain that is allosterically coupled to the putative PDZ2 domain by a network of hydrophobic interactions. This helical subdomain increases both the stability and the binding affinity of the extended PDZ structure. Using NMR and small angle neutron scattering for joint structure refinement, we demonstrate the release of intramolecular domain-domain interactions in PDZ2CT upon binding to ezrin. Based on the structural information, we show that human disease-causing mutations in PDZ2, R153Q and E225K, have significantly reduced protein stability. Loss of NHERF1 expressed in cells could result in failure to assemble membrane complexes that are important for normal physiological functions.


  • Organizational Affiliation

    New York Structural Biology Center, New York, New York 10031.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Na(+)/H(+) exchange regulatory cofactor NHE-RF1216Homo sapiensMutation(s): 0 
Gene Names: SLC9A3R1NHERFNHERF1
UniProt & NIH Common Fund Data Resources
Find proteins for O14745 (Homo sapiens)
Explore O14745 
Go to UniProtKB:  O14745
PHAROS:  O14745
GTEx:  ENSG00000109062 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14745
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Data collection, Database references, Derived calculations
  • Version 1.3: 2023-07-26
    Changes: Database references