4BG6

14-3-3 interaction with Rnd3 prenyl-phosphorylation motif


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.245 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins.

Riou, P.Kjaer, S.Garg, R.Purkiss, A.George, R.Cain, R.J.Bineva, G.Reymond, N.Mccoll, B.Thompson, A.J.O'Reilly, N.Mcdonald, N.Q.Parker, P.J.Ridley, A.J.

(2013) Cell 153: 640

  • DOI: https://doi.org/10.1016/j.cell.2013.03.044
  • Primary Citation of Related Structures:  
    4BG6

  • PubMed Abstract: 

    Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins.


  • Organizational Affiliation

    Randall Division of Cell and Molecular Biophysics, New Hunt's House, King's College London, London, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
14-3-3 PROTEIN ZETA/DELTA
A, B
245Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P63104 (Homo sapiens)
Explore P63104 
Go to UniProtKB:  P63104
PHAROS:  P63104
GTEx:  ENSG00000164924 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP63104
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
RHO-RELATED GTP-BINDING PROTEIN RHOEC [auth Q],
D [auth R]
10Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61587 (Homo sapiens)
Explore P61587 
Go to UniProtKB:  P61587
PHAROS:  P61587
GTEx:  ENSG00000115963 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61587
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.245 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.783α = 90
b = 81.313β = 90
c = 111.189γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
d*TREKdata reduction
d*TREKdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-29
    Type: Initial release
  • Version 1.1: 2019-03-13
    Changes: Data collection, Derived calculations, Experimental preparation, Other
  • Version 1.2: 2019-07-10
    Changes: Data collection
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description