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Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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G Protein-coupled Receptors01:15

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.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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G-protein Coupled Receptors01:21

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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.
GPCRs are also called heptahelical,...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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GPCRs Regulate Adenylyl Cylase Activity01:09

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Related Experiment Video

Updated: Jul 9, 2025

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Expanding the GPCR-RAMP interactome.

Ilana B Kotliar1, Annika Bendes2, Leo Dahl2

  • 1Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University; 1230 York Ave., New York, 10065, USA.

Biorxiv : the Preprint Server for Biology
|December 4, 2023
PubMed
Summary
This summary is machine-generated.

Receptor activity-modifying proteins (RAMPs) interact with G protein-coupled receptors (GPCRs), influencing their function. This study mapped these interactions, identifying 23 novel GPCR-RAMP complexes to aid therapeutic development.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology

Background:

  • Receptor activity-modifying proteins (RAMPs) modulate G protein-coupled receptor (GPCR) trafficking and pharmacology.
  • Known GPCR-RAMP interactions are limited, hindering a comprehensive understanding of their roles.

Approach:

  • Developed a library of 215 Dual Epitope-Tagged (DuET) GPCRs for comprehensive screening.
  • Employed a multiplexed suspension bead array (SBA) assay to identify GPCR-RAMP interactions.
  • Validated native interactions in three distinct cell lines.

Key Points:

  • Identified 122 GPCRs with potential interactions with at least one RAMP.
  • Confirmed native complex formation between 23 GPCRs and RAMPs.
  • Established a significant portion of the GPCR-RAMP interactome.

Conclusions:

  • This interactome mapping significantly expands the functional characterization of RAMP-interacting GPCRs.
  • Findings provide a foundation for designing targeted therapeutics for GPCR-related conditions.
  • Elucidating these complexes is crucial for understanding GPCR signaling pathways.