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Related Concept Videos

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

G-protein Coupled Receptors

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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

Transducer Mechanism: G Protein–Coupled Receptors

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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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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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Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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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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Updated: Aug 5, 2025

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
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New insights into GPCR coupling and dimerisation from cryo-EM structures.

Anastasiia Gusach1, Javier García-Nafría2, Christopher G Tate3

  • 1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 2QH, UK. Electronic address: https://twitter.com/GusachAnastasia.

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Recent advances in cryo-electron microscopy have enabled unprecedented determination of G protein-coupled receptor (GPCR) structures. This review highlights key findings in GPCR signaling, interactions, and novel methods for structural analysis.

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

  • Structural Biology
  • Biochemistry
  • Molecular Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are crucial membrane proteins involved in numerous cellular processes.
  • Recent years have seen a surge in GPCR structure determination, largely due to advancements in cryo-electron microscopy (cryo-EM).
  • Understanding GPCR structure is vital for drug discovery and deciphering complex signaling pathways.

Purpose of the Study:

  • To review significant structural insights into GPCR function gained between 2020-2022.
  • To discuss the molecular mechanisms of promiscuous G protein coupling, GPCR kinase, and β-arrestin interactions.
  • To explore novel techniques aiding the structural determination of challenging GPCR targets.

Main Methods:

  • Single-particle cryo-electron microscopy (cryo-EM) for large GPCR complexes.
  • Techniques including gene fusions, nanobodies, and Fab fragments to stabilize and visualize smaller GPCRs.
  • Analysis of structural data to understand GPCR signaling dynamics and interactions.

Main Results:

  • A significant increase in GPCR structure determination, particularly for complexes amenable to cryo-EM.
  • Detailed molecular understanding of promiscuous G protein coupling and GPCR regulation by kinases and arrestins.
  • Successful application of novel methods to determine structures of previously intractable GPCRs in inactive states.

Conclusions:

  • The past three years have revolutionized GPCR structural biology, providing unprecedented molecular detail.
  • Advances in cryo-EM and associated techniques are key to overcoming previous limitations in GPCR structure determination.
  • These structural insights are fundamental for understanding GPCR function and developing targeted therapeutics.