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Related Concept Videos

Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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 affinity and are together...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
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.
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.
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...

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Related Experiment Video

Updated: May 7, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

GPCR activation: protonation and membrane potential.

Xuejun C Zhang1, Kening Sun, Laixing Zhang

  • 1National Laboratory of Macromolecules, National Center for Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China, zhangc@ibp.ac.cn.

Protein & Cell
|September 24, 2013
PubMed
Summary
This summary is machine-generated.

G protein-coupled receptors (GPCRs) require more than just agonist binding for activation. A novel energy-coupling mechanism involving protein charge changes and membrane potential is proposed for GPCRs.

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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

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Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors (GPCRs)
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Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors (GPCRs)

Published on: February 5, 2022

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Last Updated: May 7, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

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Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors (GPCRs)
09:45

Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors (GPCRs)

Published on: February 5, 2022

Area of Science:

  • Biochemistry
  • Structural Biology
  • Cell Signaling

Background:

  • G protein-coupled receptors (GPCRs) are crucial signaling proteins involved in numerous cellular processes, diseases, and drug development.
  • While crystal structures reveal active and inactive GPCR conformations, the precise activation mechanism beyond agonist binding remains unclear.
  • Existing data suggest agonist binding alone is insufficient for initiating the conformational changes required for G-protein interaction.

Purpose of the Study:

  • To investigate the molecular determinants of GPCR activation beyond ligand binding.
  • To propose a novel mechanism explaining the conformational changes leading to GPCR activation.

Main Methods:

  • Analysis of existing GPCR crystal structures in active and inactive states.
  • Identification of conserved residues and their conformational differences.
  • Integration of structural findings with current scientific literature.

Main Results:

  • A conserved conformational switch around Asp2.50 was identified, showing distinct states in active versus inactive GPCRs.
  • This switch is proposed to be a key element in the GPCR activation process.
  • Agonist binding alone does not fully explain the observed conformational changes.

Conclusions:

  • GPCR activation involves an energy-coupling mechanism.
  • The interaction between GPCR protein charge changes and cellular membrane potential is critical for activation.
  • This finding offers new insights into GPCR signaling and potential therapeutic strategies.