Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3

Sci Rep. 2014 Nov 19;4:7115. doi: 10.1038/srep07115.

Abstract

The centromere-specific histone H3 variant, CENP-A, is overexpressed in particular aggressive cancer cells, where it can be mislocalized ectopically in the form of heterotypic nucleosomes containing H3.3. In the present study, we report the crystal structure of the heterotypic CENP-A/H3.3 particle and reveal its "hybrid structure", in which the physical characteristics of CENP-A and H3.3 are conserved independently within the same particle. The CENP-A/H3.3 nucleosome forms an unexpectedly stable structure as compared to the CENP-A nucleosome, and allows the binding of the essential centromeric protein, CENP-C, which is ectopically mislocalized in the chromosomes of CENP-A overexpressing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Autoantigens / chemistry*
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Binding Sites
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nucleosomes / chemistry*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Protein Stability
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Nucleosomes
  • Recombinant Proteins
  • centromere protein C

Associated data

  • PDB/3WTP