Related Experiment Video
Updated: Jan 18, 2026
16:36
Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
15.2K
Subtype-specific structural features of the hearing loss-associated human P2X2 receptor
Franka G Westermann1,2,3, Adam C Oken3, Philip K E Granith4
1PharmaCenter Bonn and Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, Bonn 53121, Germany.
Summary
Structural insights into the P2X2 receptor (P2X2R), an ion channel linked to hearing loss, reveal its closed and desensitized states. This research aids in developing drugs targeting P2X2R for hearing disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Structural Biology
Background:
- The P2X2 receptor (P2X2R) is an ATP-gated ion channel crucial for cochlear function.
- Mutations in P2X2R are associated with age- and noise-induced hearing loss.
- Understanding P2X2R activation and desensitization is vital for therapeutic development, yet selective modulators are scarce.
Purpose of the Study:
- To elucidate the molecular mechanisms of P2X2R activation and desensitization.
- To provide high-resolution structural data for drug development targeting P2X2R.
Main Methods:
- Cryoelectron microscopy (cryo-EM) was used to determine the structures of full-length wild-type human P2X2R.
- Structures were obtained in an apo closed state and two distinct ATP-bound desensitized states.
- Microsecond-scale molecular dynamics simulations were employed to analyze conformational changes.
Main Results:
- High-resolution cryo-EM structures of P2X2R in apo closed and two ATP-bound desensitized states were determined.
- Disease-associated mutations were localized near the transmembrane domain.
- Two distinct ATP-bound desensitized states were identified, including a novel conformation, revealing significant conformational changes in an adjacent loop.
Conclusions:
- The study provides unprecedented structural insights into the P2X2R.
- Identified conformational dynamics suggest pathways for ATP binding and release.
- These findings facilitate structure-based drug design for P2X2R, a key target for hearing loss therapies.
Keywords:
ATPcryo-EMligand-gated ion channelsmolecular dynamics (MD) simulationspurinergic P2X2 receptorMore Related Videos
05:55Dextran Labeling and Uptake in Live and Functional Murine Cochlear Hair Cells
Published on: February 8, 2020
7.9K
11:47Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
Published on: April 3, 2019
9.8K
Related Concept Videos
01:15G Protein-coupled Receptors
16.6K
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...
16.6K
01:22Hair Cells
44.4K
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
44.4K
01:13The Cochlea
50.6K
The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.
50.6K
01:30Transducer Mechanism: G Protein–Coupled Receptors
4.0K
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,...
GPCRs are also called heptahelical,...
4.0K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.8K
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...
3.8K
01:03Olfactory Receptors: Location and Structure
11.2K
The process of olfaction, also known as the sense of smell, is a sophisticated chemical response system. The specialized sensory neurons that facilitate this process, known as olfactory receptor neurons, are situated in an upper segment of the nasal cavity, known as the olfactory epithelium. Olfactory sensory neurons are bipolar, with their dendrites extending from the epithelium's apex into the mucus that lines the nasal cavity. Airborne molecules, when inhaled, traverse the olfactory...
11.2K