2BEC

Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation

Ben Ammar, Y.Takeda, S.Hisamitsu, T.Mori, H.Wakabayashi, S.

(2006) EMBO J 25: 2315-2325

  • DOI: https://doi.org/10.1038/sj.emboj.7601145
  • Primary Citation of Related Structures:  
    2BEC

  • PubMed Abstract: 

    The plasma membrane Na+/H+ exchangers (NHE) require calcineurin B homologous protein (CHP) as an obligatory binding partner for ion transport. Here, we report the first crystal structure of CHP (CHP2 isoform) in complex with its binding domain in NHE1. We show that the cytoplasmic alpha-helix of NHE1 is inserted into the hydrophobic cleft formed by N- and C-lobes of CHP2 and that the size and shape of this crevice together with hydrogen bond formation at multiple positions assure a high degree of specificity for interaction with NHE members. Structure-based mutagenesis revealed the importance of hydrophobic interactions between CHP/NHE1 for the function of NHE1. Furthermore, the crystal structure shows the existence of a protruding CHP-unique region, and deletion of this region in CHP2 inhibited the NHE1 activity by inducing the acidic shift of intracellular pH dependence, while preserving interaction with NHE1. These findings suggest that CHP serves as an obligatory subunit that is required both for supporting the basic activity and regulating the pH-sensing of NHE1 via interactions between distinct parts of these proteins.


  • Organizational Affiliation

    Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calcineurin B homologous protein 2202Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O43745 (Homo sapiens)
Explore O43745 
Go to UniProtKB:  O43745
PHAROS:  O43745
GTEx:  ENSG00000166869 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43745
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Sodium/hydrogen exchanger 143Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P19634 (Homo sapiens)
Explore P19634 
Go to UniProtKB:  P19634
PHAROS:  P19634
GTEx:  ENSG00000090020 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19634
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.220 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.262α = 90
b = 49.262β = 90
c = 102.587γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
SOLVEphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-06-27
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references, Derived calculations