Interaction of the red pigment-concentrating hormone of the crustacean Daphnia pulex, with its cognate receptor, Dappu-RPCHR: A nuclear magnetic resonance and modeling study

Jackson, Graham E.; Pavadai, Elumalai; GÄde, Gerd; Timol, Zaheer; Andersen, Niels H.

doi:10.1016/j.ijbiomac.2017.08.103

Cited by 19 publications

(44 citation statements)

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“…Similar results were found for a number of other deca-and octapeptidic members of the AKH family, i.e. for Declu-CC, Melme-CC and Dappu-RPCH (Jackson et al 2018). For each of these a -structuring was found.…”

Section: Spectral Assignmentsupporting

confidence: 82%

“…On the other hand, Schgr-AKH-II and Aedae-AKH are much more flexible. The order parameter for these two peptides range from 0.1 to 0.4, which is similar to that of Dappu-RPCH, an AKH peptide member from the crustacean water flea (Jackson et al 2018). Figure 2 shows the solution structures of the 3 AKH ligands in DPC micelle solution.…”

Section: Spectral Assignmentmentioning

confidence: 70%

“…Typically, 1 mg of sample was dissolved in 0.5 ml of either 20 mM phosphate buffer + 30% DMSO or 10:1 (v/v) H2O:D2O solution which was 150 mM in deuterated DPC-d38 (Cambridge Isotopes, 98.6% d) and buffered at pH 4.5 with 20 mM potassium phosphate buffer and an internal standard of 1% sodium 4,4-dimethyl-4-silapentane-1-sulfonate (DSS). Peptide-peptide interactions were minimized by maintaining a peptide to micelle ratio of 1:3 assuming 50 molecules of DPC per micelle (Jackson et al, 2018). Nuclear magnetic resonance (NMR) experiments were performed on a Bruker Advance 700 MHz spectrometer or Bruker Advance 600 MHz spectrometer with a prodigy probe.…”

Section: Methodsmentioning

confidence: 99%

“…This step is necessary to find better agonists, or an antagonist, in order to synthesize new analogues for testing on this system to find adequate and cheap pest insect control substances. Finally, one wants to produce cost-effective peptidomimetics which will bind specifically to the AKH R. Modelling of binding of members of the AKH/RPCH family to their cognate receptors has been undertaken before: one model has been proposed for an insect, the malaria mosquito, Anopheles gambiae (Mugumbate et al 2013), the other for a crustacean, the water flea Daphnia pulex (Jackson et al 2018). Although the receptors share spatial regions, the binding modes of the two ligands have different orientation (Jackson et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Supplemental Information 2: Raw Data for SCHGR-Akh-Ii Bound to SCHGR-Akhr in PDB Format

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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. 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 AKH receptor (AKHR) was used to construct a 3D molecular model. Next, the 3 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 (hk-OR) 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 AKH receptor 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.

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Section: Spectral Assignmentsupporting

confidence: 82%

Section: Spectral Assignmentmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Supplemental Information 2: Raw Data for SCHGR-Akh-Ii Bound to SCHGR-Akhr in PDB Format

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“…Such structure-activity studies have been conducted on the AKH system in a number of insects and a crustacean either by measuring physiological actions in vivo (Gäde and Hayes, 1995; Ziegler et al, 1998) or in a cellular mammalian expression system in vitro (Caers et al, 2012; Marchal et al, 2018; Marco et al, 2017). In conjunction with nuclear magnetic resonance (NMR) data on the secondary structure of AKHs (Nair et al, 2001; Zubrzycki and Gäde, 1994) and the knowledge of the receptor sequence, molecular dynamic methods can devise models how the ligand is interacting with its receptor (Jackson et al, 2018; Mugumbate et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

Wahedi

GÄde

Paluzzi

2019

Preprint

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G protein-coupled receptors in arthropod vectors: omics and pharmacological approaches to elucidate ligand-receptor interactions and novel organismal functions

Pietrantonio

Xiong²,

Nachman

et al. 2018

Current Opinion in Insect Science

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Regulation of many physiological processes in animals, certainly those controlled by neuropeptide hormones, involves G protein-coupled receptors (GPCRs). Our work focusing on endocrine regulation of diuresis and water balance in mosquitoes and ticks started in 1997 with the kinin receptor, at the dawn of the omics era. After the genomic revolution, we began work on the endocrinology of reproduction in the red imported fire ant. We will use the template of this comparative work to summarize key points about GPCRs and signaling, and emphasize the most recent developments in the pharmacology of arthropod neuropeptide GPCRs. We will discuss omics’ contributions to the advancement of this field, and its influence on peptidomimetic design while emphasizing work on blood feeding arthropods.

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Interaction of the red pigment-concentrating hormone of the crustacean Daphnia pulex, with its cognate receptor, Dappu-RPCHR: A nuclear magnetic resonance and modeling study

Cited by 19 publications

References 50 publications

Untitled

Untitled

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

G protein-coupled receptors in arthropod vectors: omics and pharmacological approaches to elucidate ligand-receptor interactions and novel organismal functions

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