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Cited by 6Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsTrypanosoma species research and implications

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The kinetoplastid kinetochore protein KKT23 acetyltransferase is a structural homolog of GCN5 that acetylates the histone H2A C-terminal tail

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Ludzia, Patryk, Ishii, Midori, Deák, Gauri, Spanos, Christos, Wilson, Marcus D., Redfield, Christina, Akiyoshi, Bungo·2025·Structure
DOI 10.1016/j.str.2024.10.031PMC PMC7619301

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Abstract

The kinetochore is the macromolecular protein machine that drives chromosome segregation in eukaryotes. In an evolutionarily divergent group of organisms called kinetoplastids, kinetochores are built using a unique set of proteins (KKT1-25 and KKIP1-12). KKT23 is a constitutively localized kinetochore protein containing a C-terminal acetyltransferase domain of unknown function. Here, using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we have determined the structure and dynamics of the KKT23 acetyltransferase domain from Trypanosoma brucei and found that it is structurally similar to the GCN5 histone acetyltransferase domain. We find that KKT23 can acetylate the C-terminal tail of histone H2A and that knockdown of KKT23 results in decreased H2A acetylation levels in T. brucei. Finally, we have determined the crystal structure of the N-terminal region of KKT23 and shown that it interacts with KKT22. Our study provides important insights into the structure and function of the unique kinetochore acetyltransferase in trypanosomes.

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Metadata

Authors
Ludzia, P., Ishii, M., Deák, G., Spanos, C., Wilson, M. D., Redfield, C., & Akiyoshi, B.
Affiliations
  • University of Oxford (GB)
  • Wellcome Centre for Cell Biology (GB)
Corresponding author
  • Redfield, Christina
  • Akiyoshi, Bungo
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2025-01
Volume
33
Issue
1
Pages
123-135.e10
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2024.10.031
PMC
PMC7619301
OpenAlex
W4404628429
Cited by
6
References
4
Citations by year
2026: 3 · 2025: 3
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (227243/Z/23/Z, 210493/Z/18/Z)
  • Medical Research Council (T029471/1)
  • Biotechnology and Biological Sciences Research Council (BB/M010996/1, 210622/Z/18/Z)
  • European Molecular Biology Laboratory
  • John Fell Fund, University of Oxford (226791, 108504)
  • Boehringer Ingelheim Fonds
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
Keywords
kinetochore, histone acetyltransferase, Trypanosoma brucei, kinetoplastids, chromosome segregation
MeSH terms
Protein Domains, Acetylation, Acetyltransferases, Amino Acid Sequence, Binding Sites, Histones, Models, Molecular, Protein Binding, Trypanosoma brucei brucei, Protozoan Proteins, Crystallography, X-Ray, Kinetochores, Histone Acetyltransferases

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