Related Experiment Video
Updated: May 30, 2026
10:59
Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
Published on: August 17, 2022
Conformational switches in the VPAC(1) receptor.
1Université Libre de Bruxelles, Brussels, Belgium. ilanger@ulb.ac.be
British Journal of Pharmacology
|August 3, 2011
Summary
Vasoactive intestinal peptide receptor 1 (VPAC1) activation involves a two-step ligand binding process and stabilization of receptor conformations. Understanding these mechanisms is key for VPAC1 receptor function in human physiology and disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Vasoactive intestinal peptide receptor 1 (VPAC1) is a Family B G protein-coupled receptor (GPCR) crucial for human physiology and pathophysiology.
- VPAC1 activation by VIP and pituitary AC-activating polypeptide neuropeptides follows a predicted two-domain model, but its precise mechanisms remain unclear.
- Structural differences from the well-studied GPCR-A family and lack of complete X-ray crystal structures hinder understanding of VPAC1 function.
Purpose of the Study:
- To summarize current knowledge on the molecular mechanisms of VPAC1 receptor activation and signal transduction.
- To identify amino acids critical for the two-step VIP binding process.
- To elucidate VPAC1 stabilization in inactive and active states and G protein interactions.
Main Methods:
- Literature review and knowledge synthesis on VPAC1 receptor mechanisms.
- Analysis of existing structural and biochemical data related to VPAC1 and Family B GPCRs.
- Identification of key amino acid residues through comparative analysis and functional studies.
Main Results:
- The VPAC1 receptor activation involves a sequential, two-step ligand binding mechanism.
- Specific amino acids are identified as crucial for stabilizing distinct VPAC1 receptor conformations (inactive and active).
- Understanding VPAC1-G protein interactions is essential for signal transduction pathways.
Conclusions:
- The molecular mechanisms of VPAC1 activation and signal transduction are complex, involving specific ligand binding steps and conformational stabilization.
- Further structural and functional studies are needed to fully elucidate VPAC1 receptor dynamics and its role in disease.
- This summary provides a foundation for future research into VPAC1-targeted therapeutics.
More Related Videos
08:54Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
Published on: August 9, 2024
11:19Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
Published on: July 4, 2016
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:30Transducer 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 are also called heptahelical, 7TM, or...
01:12GPCR 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...
01:21G-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.
01:21G-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.
01:15G 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...
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...