5F2U

Structure of Fully modified farnesylated INPP5E Peptide in complex with PDE6D


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 

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This is version 3.1 of the entry. See complete history


Literature

PDE6delta-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity.

Fansa, E.K.Koesling, S.K.Zent, E.Wittinghofer, A.Ismail, S.

(2016) Nat Commun 7: 11366

  • DOI: https://doi.org/10.1038/ncomms11366
  • Primary Citation of Related Structures:  
    5F2U

  • PubMed Abstract: 

    The phosphodiesterase 6 delta subunit (PDE6δ) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6δ and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6δ/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the -1 and -3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6δ and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destination.


  • Organizational Affiliation

    Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta
A, B
149Homo sapiensMutation(s): 0 
Gene Names: PDE6DPDED
UniProt & NIH Common Fund Data Resources
Find proteins for O43924 (Homo sapiens)
Explore O43924 
Go to UniProtKB:  O43924
PHAROS:  O43924
GTEx:  ENSG00000156973 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43924
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 4,5-bisphosphate 5-phosphatase, s-farnesyl-l-cysteine methyl ester
C, D
5Homo sapiensMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CMT
Query on CMT
C, D
L-PEPTIDE LINKINGC4 H9 N O2 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.47α = 90
b = 81.2β = 90
c = 117.21γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
MOLREPphasing
Cootmodel building

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-04-13
    Type: Initial release
  • Version 1.1: 2016-04-20
    Changes: Database references
  • Version 2.0: 2021-06-30
    Changes: Atomic model, Data collection, Database references, Derived calculations, Polymer sequence, Source and taxonomy, Structure summary
  • Version 3.0: 2021-07-07
    Changes: Atomic model, Data collection, Database references, Derived calculations, Polymer sequence, Source and taxonomy, Structure summary
  • Version 3.1: 2024-01-10
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description