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Related Concept Videos

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.
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G Protein-coupled Receptors01:15

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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 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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Activation and Inactivation of G Proteins01:22

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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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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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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Related Experiment Video

Updated: Oct 4, 2025

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
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Classification Model for the Second Extracellular Loop of Class A GPCRs.

Alessandro Nicoli1, Andreas Dunkel1, Toni Giorgino2

  • 1Leibniz Institute for Food Systems Biology at the Technical University of Munich, 85354 Freising, Germany.

Journal of Chemical Information and Modeling
|February 3, 2022
PubMed
Summary

The extracellular loop 2 (ECL2) in G protein-coupled receptors (GPCRs) exhibits diverse structures despite sequence variability. This study categorizes ECL2 conformations, revealing key differences and similarities across class A GPCRs.

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Area of Science:

  • Structural biology
  • Biochemistry
  • Molecular modeling

Background:

  • The extracellular loop 2 (ECL2) is a key structural component of class A G protein-coupled receptors (GPCRs).
  • ECL2 exhibits significant sequence diversity and connects transmembrane helices 4 and 5, featuring a conserved cysteine residue linked to TM3.

Purpose of the Study:

  • To analyze and categorize the structural diversity of ECL2 in class A GPCRs.
  • To understand the relationship between ECL2 sequence, shape, and intramolecular interactions.
  • To provide a reorganized structural overview of ECL2 across GPCR subfamilies.

Main Methods:

  • Analysis of experimental ECL2 structures based on sequence, shape, and intramolecular contacts.
  • Incorporation of molecular dynamics simulation data from GPCRmd.
  • Clustering of ECL2 structures based on backbone volume overlaps.

Main Results:

  • Despite high sequence variability, ECL2 structures cluster into seven distinct shape groups.
  • Conformational variations within clusters are explained by intramolecular interactions.
  • Differences and similarities in sequence and conformation were identified across class A GPCR subfamilies.

Conclusions:

  • A novel classification of ECL2 structures in class A GPCRs has been established.
  • Structural flexibility and conserved features contribute to ECL2 function.
  • This work enhances understanding of GPCR structural diversity and evolution.