Related Experiment Video
Updated: Feb 6, 2026
08:12
Expression and Purification of Mammalian Bestrophin Ion Channels
Published on: August 2, 2018
8.8K
ATP activates bestrophin ion channels through direct interaction
Yu Zhang1, Alec Kittredge1, Nancy Ward1
1Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, NY, 14642, USA.
Nature Communications
|August 9, 2018
Summary
Adenosine triphosphate (ATP) enhances human Bestrophin1 (hBest1) channel activity in retinal pigment epithelium (RPE). A specific mutation (p.I201T) impairs this ATP activation, revealing a molecular mechanism for retinal disease.
Area of Science:
- Molecular Biology
- Cell Biology
- Ophthalmology
Background:
- Human Bestrophin1 (hBest1) is a calcium-activated chloride channel crucial for retinal pigment epithelium (RPE) function.
- Mutations in hBest1 cause retinal degenerative diseases with no current treatments.
Purpose of the Study:
- To investigate the role of adenosine triphosphate (ATP) in modulating hBest1 channel activity.
- To elucidate the molecular mechanism underlying hBest1 mutations in retinal disease.
Main Methods:
- Electrophysiological recordings of hBest1 channel activity in human RPE cells.
- Biochemical assays to demonstrate direct ATP-bestrophin interaction.
- Site-directed mutagenesis to study the p.I201T mutation and its effects.
Main Results:
- ATP significantly enhances hBest1 channel activity in a dose-dependent manner.
- A direct interaction between ATP and hBest1 was identified, with an ATP-binding motif mapped to an intracellular loop.
- The disease-associated mutation p.I201T within the ATP-binding motif abrogated ATP-dependent activation and caused conformational changes.
Conclusions:
- ATP acts as a critical activator of hBest1 channels in the RPE.
- The study reveals the molecular basis for a patient-specific hBest1 mutation, highlighting the importance of ATP binding for channel function and RPE physiology.
Related Concept Videos
01:19Ion Channels
91.5K
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
91.5K
01:24Non-gated Ion Channels
8.3K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
8.3K
01:31ATP Yield
79.0K
Cellular respiration produces 30 - 32 ATP per glucose molecule. Although most of the ATP results from oxidative phosphorylation and the electron transport chain (ETC), 4 ATP are gained beforehand (2 from glycolysis and 2 from the citric acid cycle).
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
79.0K
01:12Mechanically-gated Ion Channels
7.8K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
7.8K
01:19Ligand-gated Ion Channels
14.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
14.4K
01:21G-Protein Gated Ion Channels
5.7K
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...
Sensory...
5.7K