Signaling and regulation of G-protein coupled receptors encoded by cytomegaloviruses

2004 ◽  
Vol 82 (6) ◽  
pp. 636-642 ◽  
Author(s):  
Melissa P. M Stropes ◽  
William E Miller
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
G Protein ◽  
Host Immune Response ◽  
G Protein Coupled Receptors ◽  
Molecular Regulation ◽  
Virally Encoded ◽  
Species Specific ◽  
G Protein Coupled ◽  
Insight Into

Cytomegaloviruses (CMVs) are species-specific β-herpesviruses whose replicative success is largely due to establishment of novel mechanisms for altering the host immune response. CMV encodes 3 families of putative G-protein coupled receptors (GPCRs) likely pirated from the host cell. While the functions of these virally encoded GPCRs remain unclear, the receptors possess potent signaling abilities. Understanding the molecular regulation of these GPCRs will provide important insight into CMV pathogenesis.Key words: GPCRs, HCMV, GRKs, β-arrestin, US28.

Virally Encoded G Protein-Coupled Receptors: Targets for Potentially Innovative Anti-Viral Drug Development

2003 ◽  
Vol 4 (5) ◽  
pp. 431-441 ◽  
Author(s):  
J. Smit ◽  
C. Vink ◽  
D. Verzijl ◽  
P. Casarosa ◽  
A. Bruggeman ◽  
...  
Keyword(s):  
Drug Development ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Virally Encoded ◽  
G Protein Coupled

scholarly journals Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides

2019 ◽  
Vol 116 (16) ◽  
pp. 7847-7856 ◽  
Author(s):  
Akira Shiraishi ◽  
Toshimi Okuda ◽  
Natsuko Miyasaka ◽  
Tomohiro Osugi ◽  
Yasushi Okuno ◽  
...  
Keyword(s):  
Machine Learning ◽  
G Protein ◽  
Sister Group ◽  
G Protein Coupled Receptors ◽  
Support Vector ◽  
Evolutionary Processes ◽  
Phylogenetic Tree Analysis ◽  
Species Specific ◽  
Receptor Clusters ◽  
G Protein Coupled

Neuropeptides play pivotal roles in various biological events in the nervous, neuroendocrine, and endocrine systems, and are correlated with both physiological functions and unique behavioral traits of animals. Elucidation of functional interaction between neuropeptides and receptors is a crucial step for the verification of their biological roles and evolutionary processes. However, most receptors for novel peptides remain to be identified. Here, we show the identification of multiple G protein-coupled receptors (GPCRs) for species-specific neuropeptides of the vertebrate sister group, Ciona intestinalis Type A, by combining machine learning and experimental validation. We developed an original peptide descriptor-incorporated support vector machine and used it to predict 22 neuropeptide–GPCR pairs. Of note, signaling assays of the predicted pairs identified 1 homologous and 11 Ciona-specific neuropeptide–GPCR pairs for a 41% hit rate: the respective GPCRs for Ci-GALP, Ci-NTLP-2, Ci-LF-1, Ci-LF-2, Ci-LF-5, Ci-LF-6, Ci-LF-7, Ci-LF-8, Ci-YFV-1, and Ci-YFV-3. Interestingly, molecular phylogenetic tree analysis revealed that these receptors, excluding the Ci-GALP receptor, were evolutionarily unrelated to any other known peptide GPCRs, confirming that these GPCRs constitute unprecedented neuropeptide receptor clusters. Altogether, these results verified the neuropeptide–GPCR pairs in the protochordate and evolutionary lineages of neuropeptide GPCRs, and pave the way for investigating the endogenous roles of novel neuropeptides in the closest relatives of vertebrates and the evolutionary processes of neuropeptidergic systems throughout chordates. In addition, the present study also indicates the versatility of the machine-learning–assisted strategy for the identification of novel peptide–receptor pairs in various organisms.

scholarly journals An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Joseph J Gingell ◽  
John Simms ◽  
James Barwell ◽  
David R Poyner ◽  
Harriet A Watkins ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interaction ◽  
G Protein Coupled Receptors ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Receptor Activity Modifying Proteins ◽  
G Protein Coupled ◽  
Insight Into

Abstract G protein-coupled receptors are allosteric proteins that control transmission of external signals to regulate cellular response. Although agonist binding promotes canonical G protein signalling transmitted through conformational changes, G protein-coupled receptors also interact with other proteins. These include other G protein-coupled receptors, other receptors and channels, regulatory proteins and receptor-modifying proteins, notably receptor activity-modifying proteins (RAMPs). RAMPs have at least 11 G protein-coupled receptor partners, including many class B G protein-coupled receptors. Prototypic is the calcitonin receptor, with altered ligand specificity when co-expressed with RAMPs. To gain molecular insight into the consequences of this protein–protein interaction, we combined molecular modelling with mutagenesis of the calcitonin receptor extracellular domain, assessed in ligand binding and functional assays. Although some calcitonin receptor residues are universally important for peptide interactions (calcitonin, amylin and calcitonin gene-related peptide) in calcitonin receptor alone or with receptor activity-modifying protein, others have RAMP-dependent effects, whereby mutations decreased amylin/calcitonin gene-related peptide potency substantially only when RAMP was present. Remarkably, the key residues were completely conserved between calcitonin receptor and AMY receptors, and between subtypes of AMY receptor that have different ligand preferences. Mutations at the interface between calcitonin receptor and RAMP affected ligand pharmacology in a RAMP-dependent manner, suggesting that RAMP may allosterically influence the calcitonin receptor conformation. Supporting this, molecular dynamics simulations suggested that the calcitonin receptor extracellular N-terminal domain is more flexible in the presence of receptor activity-modifying protein 1. Thus, RAMPs may act in an allosteric manner to generate a spectrum of unique calcitonin receptor conformational states, explaining the pharmacological preferences of calcitonin receptor-RAMP complexes. This provides novel insight into our understanding of G protein-coupled receptor-protein interaction that is likely broadly applicable for this receptor class.

scholarly journals G-Protein-Coupled Receptors in CNS: A Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 506 ◽  
Author(s):  
Shofiul Azam ◽  
Md. Ezazul Haque ◽  
Md. Jakaria ◽  
Song-Hee Jo ◽  
In-Su Kim ◽  
...  
Keyword(s):  
G Protein ◽  
Cognitive Deficits ◽  
Therapeutic Target ◽  
Neurological Disorders ◽  
Symptomatic Relief ◽  
Underlying Disease ◽  
G Protein Coupled Receptors ◽  
Potential Therapeutic Target ◽  
G Protein Coupled ◽  
Insight Into

Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals. Here, GPCRs’ role in the pathophysiology of different neurodegenerative disease progressions and cognitive deficits has been highlighted, and an emphasis has been placed on the current pharmacological developments with GPCRs to provide an insight into a potential therapeutic target in the treatment of neurodegeneration.

scholarly journals Computational Insight into the Ligand-Induced Conformational Specificity of G-Protein Coupled Receptors

2010 ◽  
Vol 98 (3) ◽  
pp. 290a
Author(s):  
Davide Provasi ◽  
Juan Carlos Mobarec ◽  
Marta Camacho Artacho ◽  
Marta Filizola
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Insight Into
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