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

The insulin signalling system is one of the most conserved endocrine systems of Animalia from mollusc to man. In decapod Crustacea, such as the Eastern spiny lobster, Sagmariasus verreauxi (Sv) and the red-claw crayfish, Cherax quadricarinatus (Cq), insulin endocrinology governs male sexual differen...

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Main Authors: Chandler, J., Gandhi, Neha, Mancera, Ricardo, Smith, G., Elizur, A., Ventura, T.
Format: Journal Article
Published: MDPI AG 2017
Online Access:http://hdl.handle.net/20.500.11937/56748
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author Chandler, J.
Gandhi, Neha
Mancera, Ricardo
Smith, G.
Elizur, A.
Ventura, T.
author_facet Chandler, J.
Gandhi, Neha
Mancera, Ricardo
Smith, G.
Elizur, A.
Ventura, T.
author_sort Chandler, J.
building Curtin Institutional Repository
collection Online Access
description The insulin signalling system is one of the most conserved endocrine systems of Animalia from mollusc to man. In decapod Crustacea, such as the Eastern spiny lobster, Sagmariasus verreauxi (Sv) and the red-claw crayfish, Cherax quadricarinatus (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 S. verreauxi 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 Drosophila 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 67 , G 70 , D 71 , S 72 , G 91 , G 92 , T 93 and D 94 . The significance of the negatively charged residues D 71 and D 94 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.
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spelling curtin-20.500.11937-567482018-02-12T03:37:45Z 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 Chandler, J. Gandhi, Neha Mancera, Ricardo Smith, G. Elizur, A. Ventura, T. The insulin signalling system is one of the most conserved endocrine systems of Animalia from mollusc to man. In decapod Crustacea, such as the Eastern spiny lobster, Sagmariasus verreauxi (Sv) and the red-claw crayfish, Cherax quadricarinatus (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 S. verreauxi 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 Drosophila 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 67 , G 70 , D 71 , S 72 , G 91 , G 92 , T 93 and D 94 . The significance of the negatively charged residues D 71 and D 94 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/56748 10.3390/ijms18091832 http://creativecommons.org/licenses/by/4.0/ MDPI AG fulltext
spellingShingle Chandler, J.
Gandhi, Neha
Mancera, Ricardo
Smith, G.
Elizur, A.
Ventura, T.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://hdl.handle.net/20.500.11937/56748