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Related Concept Videos

Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

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, 7TM, or...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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...
GPCR Desensitization01:12

GPCR Desensitization

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...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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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Related Experiment Video

Updated: May 29, 2026

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
09:19

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Published on: March 16, 2020

GPCR agonist binding revealed by modeling and crystallography.

Vsevolod Katritch1, Ruben Abagyan

  • 1Skaggs School of Pharmacy and Pharmaceutical Sciences and San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA 92093, USA. katritch@scripps.edu

Trends in Pharmacological Sciences
|September 10, 2011
PubMed
Summary

Computational models accurately predict G-protein-coupled receptor (GPCR) agonist binding poses and interactions. This approach aids understanding GPCR biology and drug action, complementing experimental techniques.

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Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

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Last Updated: May 29, 2026

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
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Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
16:16

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

Area of Science:

  • Structural biology
  • Computational chemistry
  • Pharmacology

Background:

  • G-protein-coupled receptors (GPCRs) are crucial membrane proteins, but their plasticity challenges structural studies, especially with agonists.
  • Predicting agonist binding and receptor changes computationally from inactive structures is vital for GPCR research and drug development.

Purpose of the Study:

  • To assess the accuracy of computational models in predicting agonist binding poses and receptor interactions for GPCRs.
  • To investigate the determinants of agonism (full, partial, inverse) using computational models with limited flexibility.

Main Methods:

  • Development and comparison of computational models with experimentally determined agonist-bound GPCR structures (β-adrenergic and adenosine A2A receptors).
  • Utilizing energy-based models with controlled backbone flexibility to analyze side-chain rotations and backbone shifts.

Main Results:

  • Computational models demonstrated high accuracy in predicting agonist binding poses (0.8 Å for β2AR, 1.7 Å for A2AAR) and receptor interactions.
  • Models successfully characterized side-chain and backbone movements in the β2AR pocket, correlating with different agonism types.

Conclusions:

  • Computational modeling is a powerful tool for predicting GPCR-ligand interactions and understanding receptor dynamics.
  • Accurate computational models will be instrumental in advancing functional and pharmacological studies of GPCRs, complementing existing experimental methods.