School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), University of Southampton, Southampton, UK.
FASEB J. 2020 Jul;34(7):8902-8919. doi: 10.1096/fj.202000545R. Epub 2020 Jun 10.
TOKs are outwardly rectifying K channels in fungi with two pore-loops and eight transmembrane spans. Here, we describe the TOKs from four pathogens that cause the majority of life-threatening fungal infections in humans. These TOKs pass large currents only in the outward direction like the canonical isolate from Saccharomyces cerevisiae (ScTOK), and distinct from other K channels. ScTOK, AfTOK1 (Aspergillus fumigatus), and H99TOK (Cryptococcus neoformans grubii) are K -selective and pass current above the K reversal potential. CaTOK (Candida albicans) and CnTOK (Cryptococcus neoformans neoformans) pass both K and Na and conduct above a reversal potential reflecting the mixed permeability of their selectivity filter. Mutations in CaTOK and ScTOK at sites homologous to those that open the internal gates in classical K channels are shown to produce inward TOK currents. A favored model for outward rectification is proposed whereby the reversal potential determines ion occupancy, and thus, conductivity, of the selectivity filter gate that is coupled to an imperfectly restrictive internal gate, permitting the filter to sample ion concentrations on both sides of the membrane.
TOKs 是真菌中具有两个孔环和八个跨膜区的外向整流钾通道。在这里，我们描述了来自四种病原体的 TOKs，这些病原体导致了大多数危及生命的人类真菌感染。这些 TOKs 仅像来自酿酒酵母（ScTOK）的典型分离物一样，在外向方向上通过大电流，与其他钾通道不同。ScTOK、AfTOK1（烟曲霉）和 H99TOK（新生隐球菌）是 K 选择性的，并在 K 反转电位以上传递电流。CaTOK（白色念珠菌）和 CnTOK（新型隐球菌）既传递 K 也传递 Na，并在反映其选择性滤器混合通透性的反转电位以上传导。在与经典钾通道内部门打开的同源位点发生突变的 CaTOK 和 ScTOK 显示产生内向 TOK 电流。提出了一种有利于外向整流的模型，其中反转电位决定了选择性滤器门的离子占据，从而决定了其导电性，该门与不完全限制的内部门偶联，允许滤器在膜的两侧对离子浓度进行采样。
