title: Prothoracicotrophic hormone has an insulin-like tertiary structure.
abstract: A three-dimensional model of PTTH-II has been constructed using interactive computer graphics and energy, minimisation techniques, assuming homology with porcine insulin, the structure of which has been determined by X-ray analysis. The model shows that PTTH-II can assume an insulin-like tertiary structure, which is compact with the exception of the sequence variable NH2-terminal amino acids of the B chain. Most of the hydrophobic core residues including A2 Ile, A6 Cys, A11 Cys, A16 Leu, A20 Cys, B11 Leu, B15 Leu and B19 Cys are identical in PTTH-II and insulins. The glycines at A1, B8 and B23 allow the chain to assume the characteristic tertiary interactions of the insulin fold and although polypeptide chains are shorter at the COOH-termini of the A and B chains and extended at the NH2-terminus of the B chain, the insulin-like tertiary structure can still be assumed. It is unlikely that PTTH-II forms either dimers or hexamers, characteristic of porcine and human insulin, and the model is consistent with the inability of PTTH-II to bind anti-insulin antibodies or insulin receptors. A hydrophobic surface region of PTTH-II may be involved in intermolecular actions of physiological relevance. We discuss the implications of our model for evolution of this family of hormones and growth factors.
authors.forename: H
authors.initials: H
authors.lastname: Jhoti
authors.forename: A N
authors.initials: AN
authors.lastname: McLeod
authors.forename: T L
authors.initials: TL
authors.lastname: Blundell
authors.forename: H
authors.initials: H
authors.lastname: Ishizaki
authors.forename: H
authors.initials: H
authors.lastname: Nagasawa
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D012831:Bombyx / Q000235:genetics; D003196:Computer Graphics; D006801:Humans; D007301:Insect Hormones / Q000235:genetics; D007328:Insulin / Q000235:genetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D013045:Species Specificity
chemical_list: D007301:Insect Hormones; D007328:Insulin; D046911:Macromolecular Substances; C009089:prothoracicotropic hormone