3FDT

Crystal structure of the complex of human chromobox homolog 5 (CBX5) with H3K9(me)3 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

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 559Homo sapiensMutation(s): 0 
Gene Names: CBX5HP1A
UniProt & NIH Common Fund Data Resources
Find proteins for P45973 (Homo sapiens)
Explore P45973 
Go to UniProtKB:  P45973
PHAROS:  P45973
GTEx:  ENSG00000094916 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45973
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
H3K9(me)3 peptideB [auth T]15synthetic constructMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P68431 (Homo sapiens)
Explore P68431 
Go to UniProtKB:  P68431
PHAROS:  P68431
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68431
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
M3L
Query on M3L
B [auth T]L-PEPTIDE LINKINGC9 H21 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.123α = 90
b = 73.123β = 90
c = 28.413γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

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