2M3O

Structure and dynamics of a human Nedd4 WW domain-ENaC complex


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

Structure and dynamics of human Nedd4-1 WW3 in complex with the alpha ENaC PY motif.

Bobby, R.Medini, K.Neudecker, P.Lee, T.V.Brimble, M.A.McDonald, F.J.Lott, J.S.Dingley, A.J.

(2013) Biochim Biophys Acta 1834: 1632-1641

  • DOI: https://doi.org/10.1016/j.bbapap.2013.04.031
  • Primary Citation of Related Structures:  
    2M3O

  • PubMed Abstract: 

    Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) is an E3 ubiquitin ligase that interacts with and negatively regulates the epithelial Na(+) channel (ENaC). The WW domains of Nedd4-1 bind to the ENaC subunits via recognition of PY motifs. Human Nedd4-1 (hNedd4-1) contains four WW domains with the third domain (WW3*) showing the strongest affinity to the PY motif. To understand the mechanism underlying this binding affinity, we have carried out NMR structural and dynamics analyses of the hNedd4-1 WW3* domain in complex with a peptide comprising the C-terminal tail of the human ENaC α-subunit. The structure reveals that the peptide interacts in a similar manner to other WW domain-ENaC peptide structures. Crucial interactions that likely provide binding affinity are the broad XP groove facilitating additional contacts between the WW3* domain and the peptide, compared to similar complexes, and the large surface area buried (83Å(2)) between R430 (WW3*) and L647' (αENaC). This corroborates the model-free analysis of the (15)N backbone relaxation data, which showed that R430 is the most rigid residue in the domain (S(2)=0.90±0.01). Carr-Purcell-Meiboom-Gill relaxation dispersion analysis identified two different conformational exchange processes on the μs-ms time-scale. One of these processes involves residues located at the peptide binding interface, suggesting conformational exchange may play a role in peptide recognition. Thus, both structural and dynamic features of the complex appear to define the high binding affinity. The results should aid interpretation of biochemical data and modeling interfaces between Nedd4-1 and other interacting proteins.


  • Organizational Affiliation

    School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase NEDD4A [auth W]43Homo sapiensMutation(s): 0 
Gene Names: NEDD4KIAA0093NEDD4-1PIG53
UniProt & NIH Common Fund Data Resources
Find proteins for P46934 (Homo sapiens)
Explore P46934 
Go to UniProtKB:  P46934
PHAROS:  P46934
GTEx:  ENSG00000069869 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP46934
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Amiloride-sensitive sodium channel subunit alphaB [auth P]11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P37088 (Homo sapiens)
Explore P37088 
Go to UniProtKB:  P37088
PHAROS:  P37088
GTEx:  ENSG00000111319 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP37088
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-28
    Type: Initial release