The amino acid sequence of the insulin from a primitive vertebrate, the atlantic hagfish (Myxine glutinosa).

Insulin has been isolated and purified from the islet organs of the cyclostome, Myxine glutinosa, by means of acid-ethanol extraction, fractional precipitation, and gel filtration. The complete amino acid sequence of the hormone has been determined by Edman degradation of the S-carboxymethylated or performic acid-oxidized A and B chains, and of various tryptic peptides derived from the chains. The 52-residue hagfish insulin has many structural features in common with other vertebrate insulins including the locations of the 6 half-cystine residues, the NH2-terminal 7 residues and the COOH-terminal 6 residues of the A chain, and several shorter sequences in the B chain that are known to comprise the dimer interface in porcine insulin crystals. Of the 24 residues which are invariant among the other known insulins, 23 are identical in hagfish int 16 of these sites it contains residues not previously observed in vertebrate insulins. The B chain also contains an additional COOH-terminal residue of methionine, making it 1 residue longer than the usual 30-residue mammalian B chains. Several features of the tertiary and quaternary structure of hagfish insulin, including the probable absence of a metal ion-stabilized hexameric form, are discussed on the basis of these findings. The results suggest that the conformation of the insulin molecule has been well conserved throughout the entire evolution of the vertebrates.