2LAJ

Third WW domain of human Nedd4L in complex with doubly phosphorylated human smad3 derived peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 300 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with acceptable covalent geometry 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A Smad action turnover switch operated by WW domain readers of a phosphoserine code.

Aragon, E.Goerner, N.Zaromytidou, A.I.Xi, Q.Escobedo, A.Massague, J.Macias, M.J.

(2011) Genes Dev 25: 1275-1288

  • DOI: https://doi.org/10.1101/gad.2060811
  • Primary Citation of Related Structures:  
    2LAJ, 2LAW, 2LAX, 2LAY, 2LAZ, 2LB0, 2LB1, 2LB2, 2LB3

  • PubMed Abstract: 

    When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events-Smad activation first and destruction later-and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains. Similarly, in the TGF-β pathway, Smad3 phosphorylation by CDK8/9 creates binding sites for Pin1 and GSK3, then adds sites to enhance Nedd4L binding. Thus, a Smad phosphoserine code and a set of WW domain code readers provide an efficient solution to the problem of coupling TGF-β signal delivery to turnover of the Smad signal transducers.


  • Organizational Affiliation

    Structural and Computational Biology Programme, Institute for Research in Biomedicine, Barcelona, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase NEDD4-like44Homo sapiensMutation(s): 1 
Gene Names: NEDD4LKIAA0439NEDL3
EC: 6.3.2
UniProt & NIH Common Fund Data Resources
Find proteins for Q96PU5 (Homo sapiens)
Explore Q96PU5 
Go to UniProtKB:  Q96PU5
PHAROS:  Q96PU5
GTEx:  ENSG00000049759 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96PU5
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Mothers against decapentaplegic homolog 310Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P84022 (Homo sapiens)
Explore P84022 
Go to UniProtKB:  P84022
PHAROS:  P84022
GTEx:  ENSG00000166949 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP84022
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
B
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 300 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with acceptable covalent geometry 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-07-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other