PURIFICATION AND STRUCTURAL CHARACTERIZATION OF INSULIN AND GLUCAGON FROM THE BICHIR POLYPTERUS-SENEGALIS (ACTINOPTERYGII, POLYPTERIFORMES)

The Polypteriformes (bichirs and reedfish) are a family of ray-finned fishes of ancient lineage. Insulin has been isolated from an extract o f the pancreas and upper gastrointestinal tract of the bichir Polypter us senegalis and its primary structure established as A-chain: )-Cys-S er-Leu-Tyr-Asp-Leu-Glu-Asn-Tyr-Cys(20)-Asn; B-chain: )-Asn-Arg-Gly-Phe -Phe-Tyr-Ile-Pro-Ser-Lys(30)-Met. Despite the fact that Polypterus ins ulin contains several unusual structural features that are not found i n insulins from other jawed fish (Asp at A-8, Thr at A-9, Arg at B-4, Asn at B-21, Ile at B-27, Met at B-31), all the residues in human insu lin that are involved in receptor binding, dimerization, and hexameriz ation have been conserved. A comparison of the structures of insulins from a range of species indicates that Polypterus insulin most closely resembles paddlefish insulin II (seven amino acid substitutions). In contrast, Polypterus glucagon g-Ala-Gln(10)-Asp-Phe-Val-Gln-Trp-Leu-Me t-Ser-Asn) most closely resembles the glucagons from the gar Lepisoste us spatula and the bowfin Amia calva (four amino acid substitutions). The data are consistent with the conclusion based on comparison of mor phological characteristics that the Polypterids are the most basal liv ing group of the Actinopterygians with evolutionary connections to bot h the Acipenserids and the Neopterygians. (C) 1998 Academic Press.