Cysteine residues in a yeast viral A/B toxin crucially control host cell killing via pH-triggered disulfide rearrangements.

ABSTRACT: K28 is a viral A/B protein toxin that intoxicates yeast and fungal cells by endocytosis and retrograde transport to the endoplasmic reticulum (ER). Although toxin translocation into the cytosol occurs on the oxidized α/β heterodimer, the precise mechanism of how the toxin crosses the ER membrane is unknown. Here we identify pH-triggered, toxin-intrinsic thiol rearrangements that crucially control toxin conformation and host cell killing. In the natural habitat and low-pH environment of toxin-secreting killer yeasts, K28 is structurally stable and biologically active as a disulfide-bonded heterodimer, whereas it forms inactive disulfide-bonded oligomers at neutral pH that are caused by activation and thiol deprotonation of β-subunit cysteines. Because such pH increase reflects the pH gradie

SUBMITTER: Suzuki Y 

PROVIDER: S-EPMC5391188 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature