THE ALLELE-SPECIFIC SYNTHETIC LETHALITY OF PRLA-PRLG DOUBLE MUTANTS PREDICTS INTERACTIVE DOMAINS OF SECY AND SECE

The secretion of proteins from the cytoplasm of Escherichia coli requi res the interaction of two integral inner membrane components, SecY an d SecE. We have devised a genetic approach to probe the molecular natu re of the SecY-SecE interaction. Suppressor alleles of secY and secE, termed prlA and prlG, respectively, were analyzed in pair-wise combina tions for synthetic phenotypes. From a total of 115 combinations, we f ound only seven pairs of alleles that exhibit a synthetic defect when present in combination with one another. The phenotypes observed are n ot the result of additive defects caused by the prl alleles, nor are t hey the consequence of multiple suppressors functioning within the sam e strain. In all cases, the synthetic defect is recessive to wild-type secY or secE provided in trans. The recessive nature argues for a def ective interaction between the Prl suppressors. The extreme allele spe cificity and topological coincidence of the mutations represented by t hese seven pairs of alleles identify domains of interaction between Se cY/PrlA and SecE/PrlG.