干旱区生态环境知识资源中心(Arid): The adipokinetic hormones and their cognate receptor from the desert locust, Schistocerca gregaria: solution structure of endogenous peptides and models of their binding to the receptor

Arid

DOI	10.7717/peerj.7514
	The adipokinetic hormones and their cognate receptor from the desert locust, Schistocerca gregaria: solution structure of endogenous peptides and models of their binding to the receptor
	Jackson, Graham E.1; Pavadai, Elumalai 1,2; Gade, Gerd 3; Andersen, Niels H.4
通讯作者	Jackson, Graham E.
来源期刊	PEERJ
ISSN	2167-8359
出版年	2019
卷号	7
英文摘要	Background: Neuropeptides exert their activity through binding to G protein-coupled receptors (GPCRs). GPCRs are well-known drug targets in the pharmaceutical industry and are currently discussed as targets to control pest insects. Here, we investigate the neuropeptide adipokinetic hormone (AKH) system of the desert locust Schistocerca gregaria. The desert locust is known for its high reproduction, and for forming devastating swarms consisting of billions of individual insects. It is also known that S. gregaria produces three different AKHs as ligands but has only one AKH receptor (AKHR). The AKH system is known to be essential for metabolic regulation, which is necessary for reproduction and flight activity. Methods: Nuclear magnetic resonance techniques (NMR) in a dodecylphosphocholin (DPC) micelle solution were used to determine the structure of the three AKHs. The primary sequence of the S. gregaria AKHR was used to construct a 3D molecular model. Next, the three AKHs were individually docked to the receptor, and dynamic simulation of the whole ligand-receptor complex in a model membrane was performed. Results: Although the three endogenous AKHs of S. gregaria have quite different amino acids sequences and chain length (two octa- and one decapeptide), NMR experiments assigned a turn structure in DPC micelle solution for all. The GPCR-ModSim program identified human kappa opioid receptor to be the best template after which the S. gregaria AKHR was modeled. All three AKHs were found to have the same binding site on this receptor, interact with similar residues of the receptor and have comparable binding constants. Molecular switches were also identified; the movement of the receptor could be visually shown when ligands (AKHs) were docked and the receptor was activated. Conclusions: The study proposes a model of binding of the three endogenous ligands to the one existing AKHR in the desert locust and paves the way to use such a model for the design of peptide analogs and finally, peptide mimetics, in the search for novel species-specific insecticides based on receptor-ligand interaction.
英文关键词	Adipokinetic hormones Schistocerca gregaria Locmi-AKH-I Aedae-AKH Schgr-AKH-II Locusta migratoria Homology modeling Agonist docking
类型	Article
语种	英语
国家	South Africa ; USA
开放获取类型	Green Published, gold, Green Submitted
收录类别	SCI-E
WOS记录号	WOS:000483309400005
WOS关键词	NUCLEAR-MAGNETIC-RESONANCE ; PIGMENT-CONCENTRATING HORMONE ; PROTEIN-COUPLED RECEPTORS ; MOLECULAR-DYNAMICS ; GENE IDENTIFICATION ; WATER SUPPRESSION ; CHEMICAL-SHIFTS ; NEUROPEPTIDE ; ACCURACY ; FAMILY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/217916
作者单位	1.Univ Cape Town, Dept Chem, Cape Town, Western Cape, South Africa; 2.Boston Univ, Dept Physiol & Biophys, Boston, MA 02215 USA; 3.Univ Cape Town, Dept Biol Sci, Cape Town, Western Cape, South Africa; 4.Univ Washington, Dept Chem, Seattle, WA 98195 USA
推荐引用方式 GB/T 7714	Jackson, Graham E.,Pavadai, Elumalai,Gade, Gerd,et al. The adipokinetic hormones and their cognate receptor from the desert locust, Schistocerca gregaria: solution structure of endogenous peptides and models of their binding to the receptor[J],2019,7.
APA	Jackson, Graham E.,Pavadai, Elumalai,Gade, Gerd,&Andersen, Niels H..(2019).The adipokinetic hormones and their cognate receptor from the desert locust, Schistocerca gregaria: solution structure of endogenous peptides and models of their binding to the receptor.PEERJ,7.
MLA	Jackson, Graham E.,et al."The adipokinetic hormones and their cognate receptor from the desert locust, Schistocerca gregaria: solution structure of endogenous peptides and models of their binding to the receptor".PEERJ 7(2019).