Mutations that detoxify an aberrant T4 membrane protein

We have investigated suppressors of the bacteriophage T4 rIIB toxic polypeptide encoded by the rIIB frameshift mutation FC238. We have found suppressors that eliminate the toxic polypeptide by creating new translational termination codons, that diminish the toxicity of the polypeptide by altering the amino acid sequence of the toxic protein, that alter the rIIA protein so as to influence toxicity, and that diminish the amount of toxic polypeptide by reducing the quantity of gene expression from the rIIB (FC238) gene. We propose that the toxicity of the FC238 polypeptide derives from its peculiar, bipartite structure and high membrane avidity. Suppressors that detoxify the FC238 polypeptide by missense probably disturb the bipartite structure and/or the affinity for the membrane. The distribution of transition mutations obtained with a variety of mutagens contributes to an appreciation of intrinsic mutability differences. Lastly, although suppressors of FC238 toxicity might emerge in phage genes other than rIIB and rIIA, none have been found.