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G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Transducer Mechanism: G Protein–Coupled Receptors01:30

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?

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Pathogens (Basel, Switzerland)
|March 26, 2025
PubMed
Summary

Cytomegaloviruses (CMVs) have unique viral G-protein-coupled receptors (vGPCRs) that differ across species. Understanding these differences is crucial for accurate CMV disease modeling and developing effective treatments.

Keywords:
G-protein coupled receptors (GPCRs)animal modelscytomegalovirus (CMV)signallingtherapeutics

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Cytomegaloviruses (CMVs) encode viral G-protein-coupled receptors (vGPCRs) that have diverged from cellular homologues.
  • Human cytomegalovirus (HCMV) encodes four vGPCRs (UL33, UL78, US27, US28) involved in pathogenesis, signaling, and latency.
  • The function of HCMV US28 is known, but other vGPCRs are less understood.

Purpose of the Study:

  • To review and highlight the differences among CMV vGPCRs.
  • To explain how these vGPCR variations impact CMV disease models.
  • To facilitate future research on CMV vGPCRs and their roles.

Main Methods:

  • Comparative analysis of vGPCRs across different CMV species (human, rodent, primate).
  • Literature review focusing on known functions and evolutionary divergence of vGPCRs.
  • Discussion of implications for translational research using animal models.

Main Results:

  • Rodent CMVs possess UL33 and UL78 homologues, while primates have additional US27 and US28 homologues.
  • CMV vGPCRs exhibit host-specific functional adaptations.
  • Significant functional and structural divergence exists between vGPCRs of different CMV strains.

Conclusions:

  • Differences in vGPCRs between CMV species necessitate careful consideration when using animal models for human CMV disease.
  • Understanding vGPCR diversity is key to improving CMV vaccine and antiviral development.
  • Further research into specific vGPCR functions will enhance the predictive value of CMV models.