The pore structure and gating mechanism of K2P channels
| Autor: | Paula L. Piechotta, Stephen J. Tucker, Thomas Baukrowitz, Phillip J. Stansfeld, Murali K. Bollepalli, Gunter Ehrlich, Hariolf Fritzenschaft, Niels Decher, Isabelle Andres-Enguix, Mark S.P. Sansom, Markus Rapedius |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
0303 health sciences
General Immunology and Microbiology General Neuroscience Intracellular pH KcsA potassium channel Gating Biology General Biochemistry Genetics and Molecular Biology Potassium channel 3. Good health Ion 03 medical and health sciences 0302 clinical medicine Protein structure Cytoplasm Biophysics Binding site Erratum Molecular Biology 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | Two-pore domain (K2P) potassium channels are important regulators of cellular electrical excitability. However, the structure of these channels and their gating mechanism, in particular the role of the bundle-crossing gate, are not well understood. Here, we report that quaternary ammonium (QA) ions bind with high-affinity deep within the pore of TREK-1 and have free access to their binding site before channel activation by intracellular pH or pressure. This demonstrates that, unlike most other K + channels, the bundle-crossing gate in this K2P channel is constitutively open. Furthermore, we used QA ions to probe the pore structure of TREK-1 by systematic scanning mutagenesis and comparison of these results with different possible structural models. This revealed that the TREK-1 pore most closely resembles the open-state structure of KvAP. We also found that mutations close to the selectivity filter and the nature of the permeant ion profoundly influence TREK-1 channel gating. These results demonstrate that the primary activation mechanisms in TREK-1 reside close to, or within the selectivity filter and do not involve gating at the cytoplasmic bundle crossing. © 2011 European Molecular Biology Organization | All Rights Reserved. |
| Databáze: | OpenAIRE |
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