Ktd1 is a phospho-regulated member of the Dup240 family that mediates defence against killer toxin K28

Ktd1 is the only Dup240 family member predominantly targeted to the vacuolar membrane and the sole protein required for defence against the K28 killer toxin in Saccharomyces cerevisiae.

• Why it matters: Dup240 proteins are highly similar yet their shared versus distinct functions in toxin defence are unclear, limiting mechanistic understanding of how this family is regulated.
• What they did: The study combined computational modelling, subcellular localisation of six family members, and liquid-based toxin sensitivity assays, then used multicopy suppressor and kinase/phosphatase screening to map regulatory inputs.
• The result: KTD1 overexpression rescued K28 sensitivity across most enzyme mutant backgrounds, while Sit4 and Hog1 emerged as key co-factors, with live-cell imaging showing no major relocalisation during K28 exposure.

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