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

Ludzia, P., Ishii, M., Deák, G., Spanos, C., Wilson, M.D., Redfield, C., and Akiyoshi, B.

By Cristina Cardenal Peralta, Discovery Research Platform for Hidden Cell Biology (DRP-HCB)

Kinetoplastids, such as Trypanosoma brucei, possess a unique kinetochore. It is built with a unique set of proteins that lack significant similarity to conventional kinetochore proteins. The kinetoplastid kinetochore proteins include KKT1-25 and KKT-interacting proteins, KKIP1-12. This study focuses on KKT23, which contains a predicted GCN5-related N-acetyltransferase (GNAT) domain at its C-terminus. In the human kinetochore, acetyl-transferases are not considered structural components, making it a unique feature of the kinetoplastid kinetochore.

Research by the Akiyoshi lab revealed that the structure of the KKT23 acetyltransferase domain is similar to that of the GCN5 histone acetyltransferase domain, as determined through NMR and crystallographic approaches. Although hyperacetylation of H2A is a known event in T. brucei, its function remained unknown. This study investigates KKT23's role in this process.

Researchers demonstrated that KKT23 specifically acetylates T. brucei nucleosomes in vitro, but not human ones. Using mass spectrometry, they identified a series of lysine residues in the H2A C-terminal tail. Furthermore, knockdown (KD) of KKT23 led to reduced levels of the H2A C-terminal tail acetylation in trypanosomes. 

Finally, using pull down and mass spectrometry approaches, researchers showed that KKT23 forms a complex with KKT22 and KKT3.

This study provides a partial answer to the poorly understood event of the H2A C-terminal tail hyperacetylation in kinetoplastids, showing that KKT23 can acetylate the H2A C-terminal tail in vitro and that its KD leads to significant decrease in acetylation levels of specific lysines in T. brucei.