Platypus insulin: indications from the amino acid sequence of significant differences in structure from porcine insulin.

Insulin from a monotreme, the platypus (Ornithorhynchus anatinus), was isolated and the amino acid sequence determined. It differs from pig insulin at eleven amino acid sites, mainly on the surface of the monomer. Substitutions relative to pig insulin occur in the monomer-monomer interface, the dimer-dimer interface and the receptor binding region. The residues A5 Glu, A8 Lys and A13 Met have not been reported before in any insulin. Multiple sequence comparison studies reveal a relatively close relationship with the nearest group of relatives to the platypus, the mammals. The relationship of the platypus sequence to reptilian insulin sequences (and amphibian and avian insulin sequences in this case) is sufficiently close to support the observation that platypus has retained some ancient reptilian characteristics over the course of evolution. Model building the platypus insulin sequence on the structure of porcine insulin indicates that there may be some interesting differences.