Molecular and Cell Biology, Saarland University, Saarbrücken, Germany.
Center of Human and Molecular Biology (ZHMB), Saarland University, Saarbrücken, Germany.
mSphere. 2020 Feb 12;5(1):e00979-19. doi: 10.1128/mSphere.00979-19.
K1 represents a heterodimeric A/B toxin secreted by virus-infected strains. In a two-staged receptor-mediated process, the ionophoric activity of K1 leads to an uncontrolled influx of protons, culminating in the breakdown of the cellular transmembrane potential of sensitive cells. K1 killer yeast necessitate not only an immunity mechanism saving the toxin-producing cell from its own toxin but, additionally, a molecular system inactivating the toxic α subunit within the secretory pathway. In this study, different derivatives of the K1 precursor were constructed to analyze the biological function of particular structural components and their influence on toxin activity as well as the formation of protective immunity. Our data implicate an inactivation of the α subunit during toxin maturation and provide the basis for an updated model of K1 maturation within the host cell's secretory pathway. The killer phenotype in the baker's yeast relies on two double-stranded RNA viruses that are persistently present in the cytoplasm. As they carry the same receptor populations as sensitive cells, killer yeast cells need-in contrast to various bacterial toxin producers-a specialized immunity mechanism. The ionophoric killer toxin K1 leads to the formation of cation-specific pores in the plasma membrane of sensitive yeast cells. Based on the data generated in this study, we were able to update the current model of toxin processing, validating the temporary inactivation of the toxic α subunit during maturation in the secretory pathway of the killer yeast.
K1 代表由病毒感染的菌株分泌的异源二聚体 A/B 毒素。在两步受体介导的过程中，K1 的离子通道活性导致质子不受控制地内流，最终导致敏感细胞的细胞跨膜电位崩溃。K1 杀伤酵母不仅需要一种免疫机制来保护产毒细胞免受自身毒素的侵害，还需要一种在分泌途径中使毒性 α 亚基失活的分子系统。在这项研究中，构建了 K1 前体的不同衍生物，以分析特定结构成分的生物学功能及其对毒素活性以及保护性免疫的影响。我们的数据表明，α 亚基在毒素成熟过程中失活，并为 K1 在宿主细胞分泌途径中成熟的更新模型提供了依据。面包酵母中的杀伤表型依赖于两种存在于细胞质中的双链 RNA 病毒。由于它们携带与敏感细胞相同的受体群体，与各种细菌毒素生产者不同，杀伤酵母细胞需要一种专门的免疫机制。离子通道杀伤毒素 K1 导致敏感酵母细胞的质膜形成阳离子特异性孔。基于本研究中获得的数据，我们能够更新当前的毒素加工模型，验证在杀伤酵母分泌途径中成熟过程中有毒的 α 亚基的暂时失活。
