The pore structure and gating mechanism of K2P channels

Autor: Paula L, Piechotta, Markus, Rapedius, Phillip J, Stansfeld, Murali K, Bollepalli, Gunter, Ehrlich, Gunter, Erhlich, Isabelle, Andres-Enguix, Hariolf, Fritzenschaft, Niels, Decher, Mark S P, Sansom, Stephen J, Tucker, Thomas, Baukrowitz
Rok vydání: 2011
Předmět:
Zdroj: The EMBO Journal
ISSN: 1460-2075
Popis: The pore structure and gating mechanism of K2P channels K2P potassium channels are important regulators of cellular excitability. This study reveals that in contrast to most other K+ channels the primary gating mechanism in the K2P channel TREK-1 does not involve opening and closure of the cytoplasmic bundle crossing, but takes place close to or within the selectivity filter.
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.
Databáze: OpenAIRE
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