Prothoracicotropic 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 NH,-terminal amino acids of the B chain. Most of the hydrophobic core residues including A2 Be, A6 Cys, Al 1 Cys, Al6 Leu, A20 Cys, Bll Leu, B15 Leu and B19 Cys are identical in PTTH-II and insulins. The glycines at Al, 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 NH,-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.

Insect prothoracicotropic hormone: a new member of the vertebrate growth factor superfamily

“…Bonabyxin, another brain secretory peptide of Bombyx that is capable of activating the prothoracic glands of the heterologous moth Samia cynthia ricini, has previously been shown to belong to the insulin family, and accordingly to be homologous with insulin-like growth factors [32,33]. This conclusion was based on the data of the amino acid sequence [34,35], disulfide bonding pattern [36], 3D structure modeling [37], and gene structure [32,38]. The present result showing that PTTH shares an ancestral molecule with the vertebrate growth factors and hCG adds to the evidence for the common origin of some hormones and growth factors, irrespective of divergence of vertebrates and invertebrates.…”

Bombyxin: An Insect Brain Peptide that Belongs to the Insulin Family

“…Five molecular forms, I, II, III, IV and V, have so far been identified from Bombyx heads (Nagasawa et al, 1984(Nagasawa et al, , 1986Jhoti et al, 1987;Maruyama et al, 1988). The primary structures have been determined completely for Fig.…”

“…Bombyxins II and IV have been chemically synthesized and proved to have the same prothoracicotropic activity in Samia as natural bombyxins Maruyama et al, 1990). Molecular modeling for the three-dimensional structure showed that bombyxin resembles insulin in adopting a globular-like core structure (Jhoti et al, 1987). Solution structure analysis of bombyxin by nuclear magnetic resonance further demonstrated that the overall main-chain fold of bombyxin is similar to those of insulin in solution, insulin in the crystalline T-state, and relaxin in the crystalline form .…”

Studies of the Structure-Activity Relationships of Peptides and Proteins Involved in Growth and Development Based on Their Three-Dimensional Structures

“…Before we determined the solution structure of bombyxin-II, its three-dimensional structure was predicted using interactive computer graphics and energy minimization techniques by assuming homology with the X-ray structure of porcine insulin. 14) In the modeled structure, the B-chain Cterminal part of bombyxin-II adopts a type-III -turn between Cys B19 and Ala B22 and an extended C-terminal segment in a way similar to insulin, but the modeled structure is not correct, at least in solution.…”