title: Importance of main-chain flexibility and the insulin fold in insulin-receptor interactions.
abstract: We have investigated the effects of altering the disposition between the COOH-terminal B chain domain of insulin and the core of the insulin molecule on ligand interactions with the hepatocyte insulin receptor. Analogues include those in which ArgB22 of des-octapeptide(B23-B30)-insulin is extended by one to three residues of glycine prior to termination in Phe-NH2, by one to five residues of glycine prior to termination in Phe-Phe-NH2, or by an additional residue of glycine prior to termination in more extended sequences derived from insulin or [GlyB24]insulin. Analogues were also examined with respect to their abilities to form hexamers in solution in the presence of Co2+, phenol, and NaSCN. Overall, our studies of ligand-receptor interactions identify that (a) the energetic penalty for the introduction of a single residue of glycine is uniform in all classes of analogues for up to three residues of glycine but diminishes somewhat for analogues with longer insertions and (b) the COOH-terminal residues of the B chain retain their importance for all classes of analogues, no matter the number of glycine residues introduced. Analogues with glycine insertions, but not those with glycine substitutions, readily form thiocyanate-stabilized complexes with Co2+ in the presence of phenol.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
authors.forename: S H
authors.initials: SH
authors.lastname: Nakagawa
authors.forename: H S
authors.initials: HS
authors.lastname: Tager
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D017510:Protein Folding; D011972:Receptor, Insulin / Q000378:metabolism*; D013552:Swine
chemical_list: D000596:Amino Acids; D007328:Insulin; D011972:Receptor, Insulin