2EZ5

Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 30 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural Determinants for High-Affinity Binding in a Nedd4 WW3(*) Domain-Comm PY Motif Complex

Kanelis, V.Bruce, M.C.Skrynnikov, N.R.Rotin, D.Forman-Kay, J.D.

(2006) Structure 14: 543-553

  • DOI: https://doi.org/10.1016/j.str.2005.11.018
  • Primary Citation of Related Structures:  
    2EZ5

  • PubMed Abstract: 

    Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn, following the PPII helical PY motif. Mutagenesis and binding studies confirm the importance of these extensive contacts, not simultaneously observed in other WW domain complexes, and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase NEDD4A [auth W]46Drosophila melanogasterMutation(s): 0 
EC: 6.3.2
UniProt
Find proteins for Q9VVI3 (Drosophila melanogaster)
Explore Q9VVI3 
Go to UniProtKB:  Q9VVI3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9VVI3
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Commissureless LPSY PeptideB [auth P]11N/AMutation(s): 0 
UniProt
Find proteins for Q24139 (Drosophila melanogaster)
Explore Q24139 
Go to UniProtKB:  Q24139
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ24139
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 30 
  • 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: 2006-03-28
    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: 2022-03-09
    Changes: Data collection, Database references, Derived calculations
  • Version 1.4: 2022-12-21
    Changes: Database references