Conserved residues in RF-NH2 receptor models identify predicted contact sites in ligand–receptor binding

Bass, Chloe; Katanski, Chris; Maynard, Benjamin F.; Zurro, I.; Mariane, E.; Matta, Michael S.; Loi, Martina; Melis, Valeria; Capponi, Valentina; Muroni, Patrizia; Setzu, Maria Dolores; Nichols, Robert C.

doi:10.1016/j.peptides.2013.06.009

Cited by 13 publications

(33 citation statements)

References 35 publications

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“…Among the repertoire of interactions between 26RFa (19–26) and the human QRFP receptor, the strongest intermolecular contact is predicted between the Arg 25 residue of the peptide and the Gln 125 residue located in the TM3 helix of the receptor (Neveu et al, ), which is known to play a key role in the structure and function of class‐A GPCR (Venkatakrishnan et al, ). Similar ligand–receptor binding interactions have been reported between two insect RFamide peptides, sulfakinin and dromyosuppressin, and their respective receptors (Bass et al, ; Rasmussen et al, ).…”

Section: Rfa/qrfp Receptor(s)supporting

confidence: 70%

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Leprince

Bagnol

Bureau

et al. 2017

British J Pharmacology

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This article, contributed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee for the QRFP receptor, confirms the existing nomenclature for this receptor, and reviews our current understanding of its structure, pharmacology and functions, and likely physiological roles in health and disease. More information on this receptor can be found in the Concise Guide to PHARMACOLOGY The RFamide neuropeptide 26RFa was first isolated from the brain of the European green frog on the basis of cross-reactivity with antibodies raised against bovine neuropeptide FF (NPFF). 26RFa and its N-terminally extended form glutamine RF-amide peptide (QRFP) have been identified as cognate ligands of the former orphan receptor GPR103, now renamed glutamine RF-amide peptide receptor (QRFP receptor). The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including humans, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei. The 26RFa/QRFP transcript is also present in various organs especially in endocrine glands. While humans express only one QRFP receptor, two isoforms are present in rodents. The QRFP receptor genes are widely expressed in the CNS and in peripheral tissues, notably in bone, heart, kidney, pancreas and testis. Structure-activity relationship studies have led to the identification of low MW peptidergic agonists and antagonists of QRFP receptor. Concurrently, several selective non-peptidic antagonists have been designed from high-throughput screening hit optimization. Consistent with the widespread distribution of QRFP receptor mRNA and 26RFa binding sites, 26RFa/QRFP exerts a large range of biological activities, notably in the control of energy homeostasis, bone formation and nociception that are mediated by QRFP receptor or NPFF2. The present report reviews the current knowledge concerning the 26RFa/QRFP-QRFP receptor system and discusses the potential use of selective QRFP receptor ligands for therapeutic applications.

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Section: Rfa/qrfp Receptor(s)supporting

confidence: 70%

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Leprince

Bagnol

Bureau

et al. 2017

British J Pharmacology

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“…To begin our studies, we predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. DrmMS-Rs are classified as members of the Rhodopsin family A receptors [ 6 ]; as such, we expected them to contain an ionic lock, 3–7 lock, transmission switch, and tyrosine toggle switch [ 1 ]. No MS-R molecular switch was previously reported in the literature.…”

Section: Resultsmentioning

confidence: 99%

“…Receptor structures were modeled by I-TASSER using multiple threading alignments zhanglab.ccmb.med.umich.edu/I-TASSER/ [ 15 ] as described [ 5 , 6 ]. The top model was submitted to ModRefiner zhanglab.ccmb.med.umich.edu/ModRefiner/ [ 16 ] after which the receptor structures were viewed in PyMOL [The PyMOL Molecular Graphics System version 1.7.0.3, Schrödinger, LLC].…”

Section: Methodsmentioning

confidence: 99%

“…Myosuppressins are members of a family of peptides with an identical C-terminal RF-NH 2 , however, the N-terminal extension is unique and differs in length and sequence [ 4 ]. The identical C terminus and variant N terminus are both important in binding and activating signaling pathways [ 5 , 6 ]. FMRF-NH 2 , the first RF-NH 2 -containing peptide isolated, was identified from a neural extract applied to a clam heart preparation [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Based on ligand-receptor contacts, analogs were predicted to be an RhpMS agonist or inactive and act as an antagonist. [ 5 – 10 ]RhpMS mimicked the full-length peptide; [ 6 – 10 ]RhpMS applied to R . prolixus heart was inactive and blocked the effect of the parent peptide.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cardiac Contractility Structure-Activity Relationship and Ligand-Receptor Interactions; the Discovery Of Unique and Novel Molecular Switches in Myosuppressin Signaling

et al. 2015

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Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS), a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR) proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs) exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR) data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3–6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (Rhp)MS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3–6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3–6 lock, transmission switch, and tyrosine toggle switch being involved in mechanisms underlying TM movement and MS-R activation, and the ability of MS agonists and antagonists to influence physiology.

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Short neuropeptide F signaling regulates functioning of male reproductive system in Tenebrio molitor beetle

et al. 2020

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Neuropeptides of short neuropeptides F family (sNPF) have been identified in various arthropods. They are pleiotropic neuromolecules which so far have been mainly associated with regulation of feeding and metabolism, as well as growth and development, locomotion, circadian rhythm or learning and memory. Here, we describe the effects of Tenebrionid sNPF peptide (SGRSPSLRLRFa) on various aspects of the male reproductive physiology in the Tenebrio molitor beetle. We identified in silico the putative sNPF receptor Tenmo-sNPFR. Based on RT-PCR technique, it was shown that the receptor might be present in the male reproductive tissues of this beetle. The analysis of receptor amino acid sequence showed that it is similar to other beetle sNPFRs, as well as other insect species, and belongs rhodopsin-like G-protein-coupled receptors (GPCRs). Injections of Trica-sNPF and its shorter form Trica-sNPF (4-11) caused differentiated effects in T. molitor male reproductive tissues. After 24 h post injections, the peptides decreased the concentration of the soluble protein fraction in testes of 4-and 8-day-old beetles as well as the dry mass of these organs but only in 8-day-old individuals. The same effects were shown with regard to accessory glands. Both peptides decrease the concentration of the soluble protein fraction but do not affect the dry mass of this organ. Furthermore, injections of Trica-sNPF at the 10-7 M concentration decrease the total sperm number in the reproductive system. Surprisingly, the same concentration of the shorter form, Trica-sNPF (4-11) increased the sperm number. It was also shown that both peptides in different manner influence contractions of ejaculatory duct. The data presented in this article give new evidence that sNPFs are involved in the regulation of reproductive events in beetles, which might be the part of a larger neuropeptide network combining feeding, growth and development with the physiology of reproduction.

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Conserved residues in RF-NH2 receptor models identify predicted contact sites in ligand–receptor binding

Cited by 13 publications

References 35 publications

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Cardiac Contractility Structure-Activity Relationship and Ligand-Receptor Interactions; the Discovery Of Unique and Novel Molecular Switches in Myosuppressin Signaling

Short neuropeptide F signaling regulates functioning of male reproductive system in Tenebrio molitor beetle

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