Closed State Structure of the Pore Revealed by Uncoupled Shaker K+ Channel
Francisco Bezanilla1, Yichen Liu1, Carlos Bassetto2
1University of Chicago.
Research Square
|May 19, 2025
Summary
Researchers uncovered the closed structure of Shaker potassium channels by uncoupling voltage sensors from the pore. This reveals a novel "roll and turn" S6 helix movement mechanism for potassium channel gating.
Area of Science:
- Structural biology
- Biophysics
- Molecular pharmacology
Background:
- Voltage-gated potassium (Kv) channels are crucial for physiological functions and are key pharmaceutical targets.
- The closed-state structure of strictly coupled Kv1 channels has remained undetermined despite advances in Kv channel structural biology.
Purpose of the Study:
- To determine the closed-state structure of the Shaker potassium channel.
- To elucidate the gating mechanism of strictly coupled Kv1 channels.
Main Methods:
- Single particle cryo-electron microscopy (cryo-EM) was used to determine the structure of an uncoupled I384R mutant Shaker potassium channel.
- Conformational transitions were analyzed from the determined structure.
Main Results:
- The structure revealed a fully closed pore with activated, non-relaxed voltage sensors.
- A novel "roll and turn" movement of S6 helices was proposed for pore domain conformational transitions.
- The permeation pathway was significantly narrowed by hydrophobic residues, and the selectivity filter adopted a noncanonical expanded state.
Conclusions:
- The study proposes a reinterpretation of the activation gating mechanism for strictly coupled Kv1 channels.
- The findings highlight the complex interactions underlying different functional states of potassium channels.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
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...
2.1K
01:24Non-gated Ion Channels
6.6K
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....
6.6K
01:19Ligand-gated Ion Channels
12.0K
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...
12.0K
01:21Structure of Porins
2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
2.9K
01:26Voltage-gated Ion Channels
7.8K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
7.8K
01:18ATP Synthase: Structure
11.8K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
11.8K