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.
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.
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DOI：
10.3390/ijms18091832
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发表时间：
2017-08-23
影响因子：
5.6
通讯作者：
Ventura T
中科院分区：
文献类型：
--
作者：
Chandler JC;Gandhi NS;Mancera RL;Smith G;Elizur A;Ventura T
胰岛素信号系统是从软体动物到人类的动物界最保守的内分泌系统之一。在十足目甲壳类动物中，例如东方大龙虾、Sagmariasus verreauxi (Sv) 和红螯虾、Cheraxquadricarinatus (Cq)，胰岛素内分泌通过雄性特异性的胰岛素样雄激素腺肽 (IAG) 的作用来控制雄性性别分化。要了解 IAG 的生物活性，有必要考虑其生物调节剂，例如胰岛素样生长因子结合蛋白 (IGFBP)。这项工作采用了各种分子建模方法来代表 S. verreauxi IGFBP 和 IAG，以及其他 Sv-ILP 配体，以表征它们的结合相互作用。首先，我们介绍 Sv- 和 Cq-ILP2：与果蝇 ILP8 (Dilp8) 具有最接近同源性的神经内分泌因子。然后，我们通过计算分析的协同作用描述了 Sv-IGFBP N 端结构域和每个 ILP 的结合相互作用。 IGFBP_N' 的深入相互作用图谱和计算丙氨酸扫描突出了热点残基 Q67、G70、D71、S72、G91、G92、T93 和 D94 的保守参与。带负电荷的残基 D71 和 D94 的重要性随后通过结构静电学进一步例证。 IGFBP 负表面电荷的功能重要性在所有三种 ILP 配体的相互结合界面上的互补正电电荷中得到了例证。经过检查，这种静电互补性与脊椎动物同系物相反。这种物理化学差异阐明了门之间的配体结合特异性。
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 Q67, G70, D71, S72, G91, G92, T93 and D94. The significance of the negatively charged residues D71 and D94 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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