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FtsK with a unique N-terminal extension is involved in coordinating the final steps of chromosome segregation with asymmetrical division in mycobacterial cells

Milcarz, K. M.; Holowka, J.; Trojanowski, D.; Lebkowski, T.; Bania, D.; Tracz, M.; Zakrzewska-Czerwinska, J. Z.

2026-01-28 molecular biology
10.64898/2026.01.27.701935 bioRxiv
Show abstract

In this study, we identify and functionally characterize a previously unrecognized, conserved N-terminal extension of mycobacterial FtsK (nFtsK) that contributes to the coordination of chromosome segregation with asymmetric cell division. Although FtsK is broadly conserved in bacteria as a late-stage DNA translocase and divisome component, mycobacterial FtsK uniquely contains a long, positively charged, intrinsically disordered N-terminal region. We show that this extension is dispensable for core FtsK functions--including septal localization, DNA translocation, and completion of cell division--but instead modulates the spatial confinement, temporal regulation, and interaction specificity of these processes. Mechanistically, nFtsK mediates specific protein interaction, binds the anionic phospholipids cardiolipin and phosphatidic acid, and exhibits intrinsic affinity for negatively curved membrane. Together, our findings uncover a lineage-specific adaptation that fine-tunes a conserved molecular machine, enhancing the robustness of asymmetric cell division in mycobacteria.

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