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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
Pore-opening mechanism in trimeric P2X receptor channels
Mufeng Li1, Toshimitsu Kawate, Shai D Silberberg
1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Mufeng_Li@nih.gov
Nature Communications
|October 27, 2010
Summary
P2X receptor channel opening involves pore-forming helices straightening upon ATP binding. This unique mechanism expands the external gate while narrowing the internal pore, impacting ion permeation.
Area of Science:
- Molecular Biology
- Structural Biology
- Neuroscience
Background:
- Ion channel gating is fundamental to biological signaling, with known mechanisms involving helix bending or tilting.
- P2X receptors are ligand-gated ion channels crucial for cellular communication.
Purpose of the Study:
- To elucidate the pore structure changes during the opening of P2X receptors.
- To investigate the gating mechanism of P2X receptors at a molecular level.
Main Methods:
- Utilized cysteine modification with thiol-reactive reagents in transmembrane helices.
- Employed engineered metal bridges to probe structural changes.
- Correlated findings with existing X-ray structures of the closed state.
Main Results:
- Demonstrated expansion of the external pore gate during channel opening.
- Observed a significant narrowing of the internal pore.
- Indicated that pore-forming helices straighten upon ATP binding.
Conclusions:
- P2X receptor gating involves a unique mechanism of helix straightening, distinct from previously described models.
- Subunit interfaces play a critical role in the gating mechanism of P2X receptors.
- The internal pore's structural changes are key to ion permeation in P2X receptors.
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