Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

12.1K
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...
12.1K
GPCR Desensitization01:12

GPCR Desensitization

6.0K
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...
6.0K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

12.1K
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...
12.1K
Lipids as Anchors01:32

Lipids as Anchors

5.6K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.6K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

2.0K
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,...
2.0K
Membrane Lipids01:32

Membrane Lipids

24.1K
Lipids are an essential component of all biological membranes. The average lipid content in mammalian membranes is 50%, though it can be as low as 20% in the inner mitochondrial membrane or as high as 80% in the myelin sheath present around the nerve cells.
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
24.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Dehydroepiandrosterone Sulfate/Cortisol Ratio as a Biomarker of Depressive Symptoms in Late-Onset Hypogonadism: An Analysis of 3,005 Males.

The world journal of men's health·2026
Same author

Structural insights into spectral tuning and retinal exchange in cone visual pigments.

Science (New York, N.Y.)·2026
Same author

Structure-guided development of a potent human B<sup>0</sup>AT1 inhibitor effective in a mouse model of phenylketonuria.

Communications biology·2026
Same author

Structural insights into YheS-mediated release of SecM-arrested ribosome.

Nature communications·2026
Same author

Structure of ergosteryl-aspartate synthase reveals how an entrapped tRNA is used like a prosthetic swinging arm in the synthesis of aminoacylated sterols.

Nature communications·2026
Same author

Structural basis and physiological significance of non-canonical G<sub>s</sub> coupling to the melatonin MT<sub>1</sub> receptor.

Nature communications·2026

Related Experiment Video

Updated: Jul 4, 2025

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
12:27

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors

Published on: June 8, 2022

3.4K

Structural basis for lysophosphatidylserine recognition by GPR34.

Tamaki Izume1, Ryo Kawahara1, Akiharu Uwamizu2

  • 1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Nature Communications
|February 7, 2024
PubMed
Summary

We determined the structure of GPR34 bound to ligands, revealing how it recognizes lysophosphatidylserine (LysoPS). This structural insight aids in developing new GPR34-targeted anticancer drugs.

More Related Videos

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

3.5K
Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

4.0K

Related Experiment Videos

Last Updated: Jul 4, 2025

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
12:27

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors

Published on: June 8, 2022

3.4K
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

3.5K
Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

4.0K

Area of Science:

  • Structural Biology
  • Pharmacology
  • Immunology

Background:

  • GPR34 is a G-protein coupled receptor with immunomodulatory functions.
  • It recognizes lysophosphatidylserine (LysoPS) as a potential ligand.

Purpose of the Study:

  • To elucidate the structural basis of GPR34 ligand recognition.
  • To provide insights for developing GPR34-targeting anticancer therapeutics.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of human GPR34-Gi complex.
  • Crystallography and molecular dynamics simulations.
  • Biochemical and physiological experiments.

Main Results:

  • Determined cryo-EM structures of human GPR34-Gi complex bound to LysoPS analogues.
  • Identified a laterally open ligand-binding pocket allowing membrane-based agonist entry.
  • Revealed specific interactions between GPR34 residues and the ligand's serine moiety and acyl chain.
  • Confirmed 2-acyl LysoPS as the likely physiological ligand for GPR34.

Conclusions:

  • The study provides high-resolution structures of GPR34 bound to its ligands.
  • These structures illuminate the mechanism of LysoPS recognition by GPR34.
  • The findings are crucial for the rational design of novel anticancer drugs targeting GPR34.