A molecular target for viral killer toxin: TOK1 potassium channels.
Killer strains of S. cerevisiae harbor double-stranded RNA viruses and secrete protein toxins that kill virus-free cells. The K1 killer toxin acts on sensitive yeast cells to perturb potassium homeostasis and cause cell death. Here, the toxin is shown to activate the plasma membrane potassium channel of S. cerevisiae, TOK1. Genetic deletion of TOK1 confers toxin resistance; overexpression increases susceptibility. Cells expressing TOK1 exhibit toxin-induced potassium flux; those without the gene do not. K1 toxin acts in the absence of other viral or yeast products: toxin synthesized from a cDNA increases open probability of single TOK1 channels (via reversible destabilization of closed states) whether channels are studied in yeast cells or X. laevis oocytes.
Ahmed
A
A
Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Sesti
F
F
Ilan
N
N
Shih
T M
TM
Sturley
S L
SL
Goldstein
S A
SA
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D018920:Coculture Techniques; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D055646:Killer Factors, Yeast; D008564:Membrane Potentials; D009183:Mycotoxins / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D012328:RNA Viruses / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology* / Q000821:virology*; D029701:Saccharomyces cerevisiae Proteins; D013104:Spheroplasts / Q000502:physiology; D014982:Xenopus laevis
D005656:Fungal Proteins; C089359:K1 killer toxin; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D015221:Potassium Channels; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C095220:TOK1 protein, S cerevisiae