3I90

Crystal structure of human chromobox homolog 6 (CBX6) with H3K27 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.252 
  • R-Value Observed: 0.254 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Recognition and specificity determinants of the human cbx chromodomains.

Kaustov, L.Ouyang, H.Amaya, M.Lemak, A.Nady, N.Duan, S.Wasney, G.A.Li, Z.Vedadi, M.Schapira, M.Min, J.Arrowsmith, C.H.

(2011) J Biol Chem 286: 521-529

  • DOI: https://doi.org/10.1074/jbc.M110.191411
  • Primary Citation of Related Structures:  
    2L11, 2L12, 2L1B, 3FDT, 3GV6, 3H91, 3I90, 3I91

  • PubMed Abstract: 

    The eight mammalian Cbx proteins are chromodomain-containing proteins involved in regulation of heterochromatin, gene expression, and developmental programs. They are evolutionarily related to the Drosophila HP1 (dHP1) and Pc (dPc) proteins that are key components of chromatin-associated complexes capable of recognizing repressive marks such as trimethylated Lys-9 and Lys-27, respectively, on histone H3. However, the binding specificity and function of the human homologs, Cbx1-8, remain unclear. To this end we employed structural, biophysical, and mutagenic approaches to characterize the molecular determinants of sequence contextual methyllysine binding to human Cbx1-8 proteins. Although all three human HP1 homologs (Cbx1, -3, -5) replicate the structural and binding features of their dHP counterparts, the five Pc homologs (Cbx2, -4, -6, -7, -8) bind with lower affinity to H3K9me3 or H3K27me3 peptides and are unable to distinguish between these two marks. Additionally, peptide permutation arrays revealed a greater sequence tolerance within the Pc family and suggest alternative nonhistone sequences as potential binding targets for this class of chromodomains. Our structures explain the divergence of peptide binding selectivity in the Pc subfamily and highlight previously unrecognized features of the chromodomain that influence binding and specificity.


  • Organizational Affiliation

    Ontario Cancer Institute, Campbell Family Cancer Research Institute and Department of Medical Biophysics, University of Toronto, Ontario M5G 1L7, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chromobox protein homolog 6
A, B
51Homo sapiensMutation(s): 0 
Gene Names: CBX6
UniProt & NIH Common Fund Data Resources
Find proteins for O95503 (Homo sapiens)
Explore O95503 
Go to UniProtKB:  O95503
PHAROS:  O95503
GTEx:  ENSG00000183741 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95503
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
H3K27 peptide
C, D
11N/AMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
M3L
Query on M3L
C, D
L-PEPTIDE LINKINGC9 H21 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.252 
  • R-Value Observed: 0.254 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.421α = 90
b = 53.421β = 90
c = 227.778γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description