Understanding Insulin Endocrinology in Decapod Crustacea: Molecular Modelling Characterization of an Insulin-Binding Protein and Insulin-Like Peptides in the Eastern Spiny Lobster, Sagmariasus verreauxi

• Published in: International journal of molecular sciences 2017-08, Vol.18 (9), p.1832
• Main Authors: Chandler, Jennifer C, Gandhi, Neha S, Mancera, Ricardo L, Smith, Greg, Elizur, Abigail, Ventura, Tomer
• Format: Article
• Language: English
• Subjects: Alanine; alanine scanning; Animals; Binding; binding interaction; Biological activity; Complementarity; Computation; Conserved Sequence; Crayfish; Crustacea; Crustacea - metabolism; decapod; Electropositivity; Electrostatic properties; Electrostatics; Endocrine system; Endocrinology; Fruit flies; Homology; hotspot residue; ILP2; Insulin; Insulin - chemistry; Insulin - metabolism; insulin-like androgenic gland peptide (IAG); insulin-like growth factor binding protein (IGFBP); Insulin-Like Growth Factor Binding Proteins - chemistry; Insulin-Like Growth Factor Binding Proteins - metabolism; insulin-like peptides (ILP1; Ligands; Molecular modelling; Mutagenesis; Peptides; Peptides - chemistry; Peptides - metabolism; Protein Binding; Regulators; Residues; Sex differentiation; Structure-function relationships; Surface charge
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18091832

The insulin signalling system is one of the most conserved endocrine systems of from mollusc to man. In decapod , such as the Eastern spiny lobster, (Sv) and the red-claw crayfish, (Cq), insulin endocrinology governs male sexual differentiation through the action of a male-specific, insulin-like androgenic gland peptide (IAG). To understand the bioactivity of IAG it is necessary to consider its bio-regulators such as the insulin-like growth factor binding protein (IGFBP). This work has employed various molecular modelling approaches to represent IGFBP and IAG, along with additional Sv-ILP ligands, in order to characterise their binding interactions. Firstly, we present Sv- and Cq-ILP2: neuroendocrine factors that share closest homology with ILP8 (Dilp8). We then describe the binding interaction of the N-terminal domain of Sv-IGFBP and each ILP through a synergy of computational analyses. In-depth interaction mapping and computational alanine scanning of IGFBP_N' highlight the conserved involvement of the hotspot residues Q , G , D , S , G , G , T and D . The significance of the negatively charged residues D and D was then further exemplified by structural electrostatics. The functional importance of the negative surface charge of IGFBP is exemplified in the complementary electropositive charge on the reciprocal binding interface of all three ILP ligands. When examined, this electrostatic complementarity is the inverse of vertebrate homologues; such physicochemical divergences elucidate towards ligand-binding specificity between Phyla.