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Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
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Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1
Julia Kowal1, Mohamed Chami1, Paul Baumgartner1
1Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Nature Communications
|January 29, 2014
Summary
Cyclic nucleotide binding causes conformational changes in MloK1 potassium channels. This structural insight reveals how ligand binding may directly influence channel opening, aiding eukaryotic pacemaking research.
Area of Science:
- Structural biology
- Biophysics
- Molecular biology
Background:
- Cyclic nucleotide-modulated ion channels are crucial for eukaryotic signal transduction and pacemaking.
- Understanding the molecular basis of ligand gating in these channels is limited by a lack of structural data.
Purpose of the Study:
- To investigate ligand-induced conformational changes in the MloK1 potassium channel.
- To elucidate the structural mechanisms underlying cyclic nucleotide-modulated channel gating.
Main Methods:
- Electron crystallography
- Atomic force microscopy
- Analysis of full-length MloK1 channel structure
Main Results:
- cAMP binding induces vertical movement of cyclic nucleotide-binding domains towards the membrane.
- Ligand binding leads to direct contact between cyclic nucleotide-binding domains and voltage sensor domains.
- Voltage sensor domain helices undergo significant shifts and tilts, while the pore remains open.
Conclusions:
- Ligand binding favors channel pore opening through direct interaction with voltage sensors.
- A mechanistic hypothesis for coupling ligand gating and voltage sensing in eukaryotic HCN channels is proposed.
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