Family B G Protein-coupled Receptors and their Ligands: From Structure to Function

Liapakis, George; Matsoukas, Minos‐Timotheos; Karageorgos, Vlasios; Venihaki, Maria; Mavromoustakos, Thomas

doi:10.2174/0929867324666170303162416

Cited by 12 publications

(8 citation statements)

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“…The B1 subfamily is made of largely classical hormone receptors. It comprises three types of hormone receptors in D. melanogaster: diuretic hormone 31 receptor (DH31-R/hector), CRF-like diuretic hormone 44 (DH44-R), and pigment dispersing factor receptor (Pdfr) (57)(58)(59)(60). In our study, all three types of hormone receptors were identified.…”

Section: Family-b Gpcrsmentioning

confidence: 71%

Identification and Expression Analysis of G Protein-Coupled Receptors in the Miridae Insect Apolygus lucorum

Gao

Wang

et al. 2021

Front. Endocrinol.

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G protein-coupled receptors (GPCRs) are the largest and most versatile family of transmembrane receptors in the cell and they play a vital role in the regulation of multiple physiological processes. The family Miridae (Hemiptera: Heteroptera) is one of the most diverse families of insects. Until now, information on GPCRs has been lacking in Miridae. Apolygus lucorum, a representative species of the Miridae, is an omnivorous pest that occurs worldwide and is notorious for causing serious damage to various crops and substantial economic losses. By searching the genome, 133 GPCRs were identified in A. lucorum. Compared with other model insects, we have observed GPCR genes to be remarkably expanded in A. lucorum, especially focusing on biogenic amine receptors and neuropeptide receptors. Among these, there is a novel large clade duplicated from known FMRFamide receptors (FMRFaRs). Moreover, the temporal and spatial expression profiles of the 133 genes across developmental stages were determined by transcriptome analysis. Most GPCR genes showed a low expression level in the whole organism of A. lucorum. However, there were a few highly expressed GPCR genes. The highly expressed LW opsins in the head probably relate to nocturning of A. lucorum, and the expression of Cirl at different times and in different tissues indicated it may be involved in growth and development of A. lucorum. We also found C2 leucine-rich repeat-containing GPCRs (LGRs) were mainly distributed in Hemiptera and Phthiraptera among insects. Our study was the first investigation on GPCRs in A. lucorum and it provided a molecular target for the regulation and control of Miridae pests.

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Section: Family-b Gpcrsmentioning

confidence: 71%

Identification and Expression Analysis of G Protein-Coupled Receptors in the Miridae Insect Apolygus lucorum

Gao

Wang

et al. 2021

Front. Endocrinol.

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“…As is the case for all GPCRs, the GLP-1R consists of an extracellular N-terminal domain (N-domain), an intracellular C-terminal region, and seven TMs that are connected to each other by three extracellular loops (ELs) and also three intracellular loops (10,69). The ELs and TMs form the J-domain of receptor that binds GLP-1.…”

Section: Computational Modeling Predicts Conserved Features Of Ligandmentioning

confidence: 99%

Nonconventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput FRET assays for cAMP

Chepurny

Matsoukas

Liapakis

et al. 2019

Journal of Biological Chemistry

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Edited by Jeffrey E. Pessin G protein-coupled receptors (GPCRs) for glucagon (GluR) and glucagon-like peptide-1 (GLP-1R) are normally considered to be highly selective for glucagon and GLP-1, respectively. However, glucagon secreted from pancreatic ␣-cells may accumulate at high concentrations to exert promiscuous effects at the ␤-cell GLP-1R, as may occur in the volume-restricted microenvironment of the islets of Langerhans. Furthermore, systemic administration of GluR or GLP-1R agonists and antagonists at high doses may lead to off-target effects at other receptors. Here, we used molecular modeling to evaluate data derived from FRET assays that detect cAMP as a read-out for GluR and GLP-1R activation. This analysis established that glucagon is a nonconventional GLP-1R agonist, an effect inhibited by the GLP-1R orthosteric antagonist exendin(9 -39) (Ex(9 -39)). The GluR allosteric inhibitors LY2409021 and MK 0893 antagonized glucagon and GLP-1 action at the GLP-1R, whereas des-His 1 -[Glu 9 ]glucagon antagonized glucagon action at the GluR, while having minimal inhibitory action versus glucagon or GLP-1 at the GLP-1R. When testing Ex(9 -39) in combination with des-His 1 -[Glu 9 ]glucagon in INS-1 832/13 cells, we validated a dual agonist action of glucagon at the GluR and GLP-1R. Hybrid peptide GGP817containing glucagon fused to a fragment of peptide YY (PYY) acted as a triagonist at the GluR, GLP-1R, and neuropeptide Y2 receptor (NPY2R). Collectively, these findings provide a new triagonist strategy with which to target the GluR, GLP-1R, and NPY2R. They also provide an impetus to reevaluate prior studies in which GluR and GLP-1R agonists and antagonists were assumed not to exert promiscuous actions at other GPCRs.

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“…Of the 826 human GPCRs, 118 are recognized as endogenous peptide or protein ligands. 10 To date, besides the class B structures binding to α-helical peptides, 11 only a few published crystal structures of class A GPCRs bound to peptides including the neurotensin receptor 1 (NTSR1) bound to NTS, 12 the chemokine receptor CXCR4 in complex with a cyclic peptide agonist 13 and a viral chemokine, 14 and the angiotensin II type 2 receptor bound to an angiotensin II analogue. 15 However, there is no conserved structural information of peptides binding to GPCRs because of their diversity in sequence, size, and conformation.…”

Section: Introductionmentioning

confidence: 99%

Combined Computational and Structural Approach into Understanding the Role of Peptide Binding and Activation of Melanocortin Receptor 4

Zachmann

Kritsi

Tapeinou

et al. 2020

J. Chem. Inf. Model.

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Melanocortin receptor 4 (MC4R) is expressed predominantly in the central nervous system and regulates food intake and sexual function and is also thought to be responsible for effects on mood and cognition. It belongs to the melanocortin receptor subfamily of G protein-coupled receptors (GPCRs). Here, we have synthesized and structurally characterized three peptides that bind to MC4R, producing different signaling events. AgRP is a naturally occurring antagonist, HLWNRS is the minimal sequence of the N-terminal with partial agonist activity, and aMSH is a full agonistic peptide. By implementing molecular dynamics simulations on the different peptide−receptor complexes, we propose their molecular basis of binding to investigate their differential molecular properties regarding the activation states of the receptor. Our analysis shows that the agonist and partial agonist may induce rotation in transmembrane helix 3, which is known to be involved in the key events occurring during GPCR activation, and this movement is impacted by certain aromatic residues and their positioning in the orthosteric binding site of the receptor.

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Family B G Protein-coupled Receptors and their Ligands: From Structure to Function

Cited by 12 publications

References 0 publications

Identification and Expression Analysis of G Protein-Coupled Receptors in the Miridae Insect Apolygus lucorum

Identification and Expression Analysis of G Protein-Coupled Receptors in the Miridae Insect Apolygus lucorum

Nonconventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput FRET assays for cAMP

Combined Computational and Structural Approach into Understanding the Role of Peptide Binding and Activation of Melanocortin Receptor 4

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