Escherichia coli Heat - labile Enterotoxin NUCLEOTIDE SEQUENCE

We report the complete DNA sequence of the Escherichia coli elt A gene, which codes for the A subunit of the heat-labile enterotoxin, LT. The amino acid sequence of the LT A subunit has been deduced from the DNA sequence of elt A. The LT A subunit starts with methionine, ends with leucine, and comprises 264 amino acids. The computed molecular weight of LT A is 29,673. The A subunit of cholera toxin (CT A) has been shown to be structurally and functionally related to the LT A subunit. Comparison of the primary structure of LT A with the known partial amino acid sequence of CT A indicates that the 2 polypeptides share considerable homology throughout their sequences. The NHz-terminal regions exhibit the highest degree of homology (91%), while the COOH-terminal region, containing the sole cystine residue in each toxin is less conserved (-52%). Alignment of homologous residues in the COOH-terminal regions of LT A and CT A indicates that a likely site for proteolytic cleavage of LT A is after Arg residue 188. The resulting Az polypeptide would be 46 amino acids long, would contain a single cysteine residue, and have M, = 5261. The elt A nucleotide sequence further predicts that the LT A protein is synthesized in a precursor form, possessing an 18amino acid signal sequence at its N H 2 terminus.