Prothoracicotrophic hormone has an insulin-like tertiary structure.

Area of Science:

• Structural Biology
• Endocrinology
• Evolutionary Biology

Background:

• Insect prothoracicotropic hormone II (PTTH-II) is a crucial neurohormone regulating molting and metamorphosis.
• The tertiary structure of PTTH-II has not been experimentally determined, limiting understanding of its function and evolutionary relationships.
• Insulin and insulin-like growth factors (IGFs) are well-characterized hormones with known three-dimensional structures and biological functions.

Purpose of the Study:

• To construct and analyze a three-dimensional model of PTTH-II based on homology with porcine insulin.
• To investigate the potential for PTTH-II to adopt an insulin-like tertiary structure.
• To explore the evolutionary implications of PTTH-II's structure in relation to insulins and growth factors.

Main Methods:

• Construction of a PTTH-II three-dimensional model using interactive computer graphics.
• Application of energy minimization techniques to refine the model structure.
• Comparative analysis of PTTH-II model with the X-ray determined structure of porcine insulin.

Main Results:

• The PTTH-II model demonstrates an insulin-like tertiary structure, characterized by a compact hydrophobic core.
• Key hydrophobic residues crucial for the insulin fold are conserved between PTTH-II and insulins.
• Despite variations in chain termini, PTTH-II can assume the characteristic insulin fold; it is unlikely to form dimers/hexamers and cannot bind insulin antibodies or receptors.

Conclusions:

• PTTH-II possesses an insulin-like tertiary structure, suggesting a shared evolutionary origin with insulins and IGFs.
• Structural similarities, particularly in the hydrophobic core, underpin the functional and evolutionary relationships within this hormone family.
• The model provides insights into the evolution of hormones and growth factors, highlighting conserved structural motifs despite sequence divergence.