An Iml3-Chl4 heterodimer links the core centromere to factors required for accurate chromosome segregation

Cell Rep. 2013 Oct 17;5(1):29-36. doi: 10.1016/j.celrep.2013.08.036. Epub 2013 Sep 26.


Accurate segregation of genetic material in eukaryotes relies on the kinetochore, a multiprotein complex that connects centromeric DNA with microtubules. In yeast and humans, two proteins-Mif2/CENP-C and Chl4/CNEP-N-interact with specialized centromeric nucleosomes and establish distinct but cross-connecting axes of chromatin-microtubule linkage. Proteins recruited by Chl4/CENP-N include a subset that regulates chromosome transmission fidelity. We show that Chl4 and a conserved member of this subset, Iml3, both from Saccharomyces cerevisiae, form a stable protein complex that interacts with Mif2 and Sgo1. We have determined the structures of an Iml3 homodimer and an Iml3-Chl4 heterodimer, which suggest a mechanism for regulating the assembly of this functional axis of the kinetochore. We propose that at the core centromere, the Chl4-Iml3 complex participates in recruiting factors, such as Sgo1, that influence sister chromatid cohesion and encourage sister kinetochore biorientation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Centromere / genetics*
  • Centromere / metabolism
  • Chromosome Segregation*
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Point Mutation
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism


  • CHL4 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • IML3 protein, S cerevisiae
  • MIF2 protein, S cerevisiae
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Sgo1 protein, S cerevisiae

Associated data

  • PDB/4IT3
  • PDB/4JE3