1I5H

SOLUTION STRUCTURE OF THE RNEDD4 WWIII DOMAIN-RENAL BP2 PEPTIDE COMPLEX


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 170 
  • Conformers Submitted: 15 
  • 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

Solution structure of a Nedd4 WW domain-ENaC peptide complex.

Kanelis, V.Rotin, D.Forman-Kay, J.D.

(2001) Nat Struct Biol 8: 407-412

  • DOI: https://doi.org/10.1038/87562
  • Primary Citation of Related Structures:  
    1I5H

  • PubMed Abstract: 

    Nedd4 is a ubiquitin protein ligase composed of a C2 domain, three (or four) WW domains and a ubiquitin ligase Hect domain. Nedd4 was demonstrated to bind the epithelial sodium channel (alphabetagammaENaC), by association of its WW domains with PY motifs (XPPXY) present in each ENaC subunit, and to regulate the cell surface stability of the channel. The PY motif of betaENaC is deleted or mutated in Liddle syndrome, a hereditary form of hypertension caused by elevated ENaC activity. Here we report the solution structure of the third WW domain of Nedd4 complexed to the PY motif-containing region of betaENaC (TLPIPGTPPPNYDSL, referred to as betaP2). A polyproline type II helical conformation is adopted by the PPPN sequence. Unexpectedly, the C-terminal sequence YDSL forms a helical turn and both the tyrosine and the C-terminal leucine contact the WW domain. This is unlike other proline-rich peptides complexed to WW domains, which bind in an extended conformation and lack molecular interactions with residues C-terminal to the tyrosine or the structurally equivalent residue in non-PY motif WW domain targets. The Nedd4 WW domain-ENaC betaP2 peptide structure expands our understanding of the mechanisms involved in WW domain-ligand recognition and the molecular basis of Liddle syndrome.


  • Organizational Affiliation

    Programmes in Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UBIQUITIN LIGASE NEDD4A [auth W]50Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for Q62940 (Rattus norvegicus)
Explore Q62940 
Go to UniProtKB:  Q62940
Entity Groups  
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UniProt GroupQ62940
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
AMILORIDE-SENSITIVE SODIUM CHANNEL BETA-SUBUNIT17Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P37090 (Rattus norvegicus)
Explore P37090 
Go to UniProtKB:  P37090
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP37090
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 170 
  • Conformers Submitted: 15 
  • 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: 2001-05-02
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-23
    Changes: Database references, Derived calculations