3V2X

Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock.

Xu, C.Jin, J.Bian, C.Lam, R.Tian, R.Weist, R.You, L.Nie, J.Bochkarev, A.Tempel, W.Tan, C.S.Wasney, G.A.Vedadi, M.Gish, G.D.Arrowsmith, C.H.Pawson, T.Yang, X.J.Min, J.

(2012) Sci Signal 5: ra39-ra39

  • DOI: https://doi.org/10.1126/scisignal.2002979
  • Primary Citation of Related Structures:  
    3SO8, 3UXG, 3UZD, 3V2O, 3V2X, 3V30, 3V31

  • PubMed Abstract: 

    Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ankyrin repeat family A protein 2167Homo sapiensMutation(s): 0 
Gene Names: ANKRAANKRA2
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H9E1 (Homo sapiens)
Explore Q9H9E1 
Go to UniProtKB:  Q9H9E1
PHAROS:  Q9H9E1
GTEx:  ENSG00000164331 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H9E1
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Low-density lipoprotein receptor-related protein 211Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P98158 (Rattus norvegicus)
Explore P98158 
Go to UniProtKB:  P98158
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP98158
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 29.962α = 78.51
b = 32.75β = 75.17
c = 45.314γ = 65.95
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
JDirectordata collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-04
    Type: Initial release
  • Version 1.1: 2012-06-13
    Changes: Database references
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Refinement description