Structure of the Fission Yeast Meiotic Driver Tdk1 Bound to Bdf1
From Proteopedia
Contents |
Tdk1-Bdf1 Complex (Cryo-EM Structure)
The Tdk1–Bdf1 complex captures the molecular mechanism by which the selfish meiotic driver Tdk1 hijacks the epigenetic reader Bdf1 in Schizosaccharomyces pombe. Tdk1 binds directly to the Bdf1 bromodomain, blocking its ability to engage acetylated histones and disrupting chromosome segregation in noncarrier spores. The cryo-EM structure (PDB ID 9JA5) shows how Tdk1 reshapes the Bdf1 acetyl-lysine pocket, providing a structural explanation for meiotic drive–induced mitotic failure.
The Structure
| |||||||||||
Biological Significance
Tdk1 hijacks Bdf1 during spore germination, forming stable nuclear foci that create abnormal chromosomal adhesions, disrupting mitosis in noncarrier progeny. Killer Meiotic Elements like Tdk1 are also known to bias Mendelian inheritance. The study also found the HT3 variant which has mutations in the interacting regions showing how loss of interaction evolves resistant, non-killing haplotypes.
Methods
Cryo-EM single-particle analysis, proximity labeling, genetics, and yeast-2-hybrid were used to define the function of Tdk1 and its interaction with Bdf1.
References
1. Hua, Y., Zhang, J., Yang, M.Y., Zhang, F.Y., Ren, J.Y., Lyu, X.H., Ding, Y., Suo, F., Shao, G.C., Li, J. and Dong, M.Q., 2024. A meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring. Proceedings of the National Academy of Sciences, 121(45), p.e2408347121.
2. Hua, Y., Zhang, J., Yang, M.Y., Ren, J.Y., Suo, F., Liang, L., Dong, M.Q., Ye, K. and Du, L.L., 2024. Structural duality enables a single protein to act as a toxin–antidote pair for meiotic drive. Proceedings of the National Academy of Sciences, 121(45), p.e2408618121.
Course code: BI3323-Aug2025
