1JMQ

YAP65 (L30K mutant) WW domain in Complex with GTPPPPYTVG peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • 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

Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope.

Pires, J.R.Taha-Nejad, F.Toepert, F.Ast, T.Hoffmuller, U.Schneider-Mergener, J.Kuhne, R.Macias, M.J.Oschkinat, H.

(2001) J Mol Biol 314: 1147-1156

  • DOI: https://doi.org/10.1006/jmbi.2000.5199
  • Primary Citation of Related Structures:  
    1JMQ, 1K9Q, 1K9R

  • PubMed Abstract: 

    The single mutation L30 K in the Hu-Yap65 WW domain increased the stability of the complex with the peptide GTPPPPYTVG (K(d)=40(+/-5) microM). Here we report the refined solution structure of this complex by NMR spectroscopy and further derived structure-activity relationships by using ligand peptide libraries with truncated sequences and a substitution analysis that yielded acetyl-PPPPY as the smallest high-affinity binding peptide (K(d)=60 microM). The structures of two new complexes with weaker binding ligands chosen based on these results (N-(n-octyl)-GPPPYNH(2) and Ac-PLPPY) comprising the wild-type WW domain of Hu-Yap65 were determined. Comparison of the structures of the three complexes were useful for identifying the molecular basis of high-affinity: hydrophobic and specific interactions between the side-chains of Y28 and W39 and P5' and P4', respectively, and hydrogen bonds between T37 (donnor) and P5' (acceptor) and between W39 (donnor) and T2' (acceptor) stabilize the complex.The structure of the complex L30 K Hu-Yap65 WW domain/GTPPPPYTVG is compared to the published crystal structure of the dystrophin WW domain bound to a segment of the beta-dystroglycan protein and to the solution structure of the first Nedd4 WW domain and its prolin-rich ligand, suggesting that WW sequences bind proline-rich peptides in an evolutionary conserved fashion. The position equivalent to T22 in the Hu-Yap65 WW domain sequence is seen as responsible for differentiation in the binding mode among the WW domains of group I.


  • Organizational Affiliation

    Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125 Berlin, Germany. oschkinat@fmp-berlin.de


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
65 KDA YES-ASSOCIATED PROTEIN46Homo sapiensMutation(s): 1 
Gene Names: YAP65
UniProt & NIH Common Fund Data Resources
Find proteins for P46937 (Homo sapiens)
Explore P46937 
Go to UniProtKB:  P46937
PHAROS:  P46937
GTEx:  ENSG00000137693 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP46937
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
WW Domain Binding Protein-1B [auth P]10N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q96G27 (Homo sapiens)
Explore Q96G27 
Go to UniProtKB:  Q96G27
GTEx:  ENSG00000239779 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96G27
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • 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: 2001-12-21
    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: 2021-10-27
    Changes: Data collection, Database references, Derived calculations