Recognition of centromere-specific histone Cse4 by the inner kinetochore Okp1-Ame1 complex

EMBO Rep. 2023 Dec 6;24(12):e57702. doi: 10.15252/embr.202357702. Epub 2023 Nov 20.

Abstract

Successful mitosis depends on the timely establishment of correct chromosomal attachments to microtubules. The kinetochore, a modular multiprotein complex, mediates this connection by recognizing specialized chromatin containing a histone H3 variant called Cse4 in budding yeast and CENP-A in vertebrates. Structural features of the kinetochore that enable discrimination between Cse4/CENP-A and H3 have been identified in several species. How and when these contribute to centromere recognition and how they relate to the overall structure of the inner kinetochore are unsettled questions. More generally, this molecular recognition ensures that only one kinetochore is built on each chromatid and that this happens at the right place on the chromatin fiber. We have determined the crystal structure of a Cse4 peptide bound to the essential inner kinetochore Okp1-Ame1 heterodimer from budding yeast. The structure and related experiments show in detail an essential point of Cse4 contact and provide information about the arrangement of the inner kinetochore.

Keywords: X-ray crystallography; centromere; kinetochore; mitosis.

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Centromere / metabolism
  • Centromere Protein A / metabolism
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics
  • Histones / metabolism
  • Kinetochores / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomycetales* / metabolism

Substances

  • Cell Cycle Proteins
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histones
  • Saccharomyces cerevisiae Proteins
  • CSE4 protein, S cerevisiae
  • Okp1 protein, S cerevisiae
  • Ame1 protein, S cerevisiae