1.C.6 The Yeast Killer Toxin K1 (YKT-K1) Family
A single, well-characterized yeast killer toxin, K1, produced by Saccharomyces cerevisiae killer strains that bear the specific satellite dsRNA which encodes the killer toxin, comprises the YKT-K1 family. A strain that produces the toxin is resistant to it, but other yeast strains are sensitive. The toxin is made as a preprotoxin which is processed during secretion via the endoplasmic reticulum, Golgi apparatus and secretory vesicles to yield the mature, active extracellular toxin.
K1 (19 kDa) is the best studied yeast killer toxin. It consists of two distinct, disulfide-bonded, unglycosylated subunits, α(9.5 kDa) and β (9.0 kDa) derived from a glycosylated 42 kDa protoxin. The protoxin is derived from the dsRNA-encoded, 316 amino acyl, 35 kDa preprotoxin M1p. The preprotoxin consists of an N-terminal 44 amino acyl leader sequence (δ), including a 26 amino acyl signal peptide, the 103 residue α-domain (positions 45-147), an 85 residue γ-peptide and the 83 residue β-domain (positions 234-316). The α- and β-subunits are disulfide-bonded in the mature toxin.
K1 kills susceptible yeast cells by (1) binding to a cell wall receptor, (2) binding to a membrane receptor, (3) inserting into the cytoplasmic membrane and (4) forming a voltage-independent cation-selective transmembrane channel which causes ion leakage and subsequent cell death. Two strongly hydrophobic regions near the C-terminus of the α-subunit (residues 72-91 and 112-130) form α-helical structures that presumably insert into the membrane to form the oligomeric channel. Some other nonhomologous yeast killer toxins are believed to function as channels, but many others kill target yeast cells by unrelated mechanisms.
K1 toxin is encoded by a yeast viral gene and targets virus-free cells. K1 is known to produce uncontrolled leakage of K+, H+, ATP, and other small molecules from the target cell. Recently it has been suggested that the major killing effect is due to the loss of K+, and that the toxin functions in this capacity by activating the yeast TOK1 K+ channel rather than (or in addition to) forming a transmembrane channel (Ahmed et al., 1999).
The generalized transport reaction catalyzed by yeast killer toxin K1 is:
ions (in) ions (out).