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

Armstrong

Ashmole

Barel

Baukrowitz

Bayliss

Ben-Abu

Chemin

Choi

Clarke

Cohen

Contreras

Cuello

Demo

Enyedi

Goodsell

Gunter Erhlich

Hariolf Fritzenschaft

Heurteaux

Hibino

Holmgren

Honore

Isabelle Andres-Enguix

Kollewe

Lafreniere

Lotshaw

Loussouarn

Maingret

Mark S P Sansom

Markus Rapedius

Mathie

Milac

Murali K Bollepalli

Niels Decher

Niemeyer

Oliver

Paula L Piechotta

Phillip J Stansfeld

Phillips

Piskorowski

Rapedius

Sali

Sandoz

Schroeder

Schulte

Stansfeld

Stephen J Tucker

Streit

Swartz

Thomas Baukrowitz

Treptow

Wilkens

Yellen

Zhang

Zhou

Zilberberg

The EMBO Journal

English

PubMed

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

Piechotta, PL

Rapedius, M

Stansfeld, PJ

Bollepalli, MK

Ehrlich, G

Erhlich, G

Andres-Enguix, I

Fritzenschaft, H

Decher, N

Sansom, MS

Tucker, Stephen

Baukrowitz, T

Oxford University Research Archive

The pore structure and gating mechanism of K2P channels.

Sansom, MSP

Tucker, SJ

Oxford University Research Archive (ORA)

The pore structure and gating mechanism of K2P channels (vol 30, pg 3607, 2011)

ORA - Oxford University Research Archive

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

Sansom, Mark

The pore structure and gating mechanism of K2P channels

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3230381

The pore structure and gating mechanism of K2P channels

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Oxford University Research Archive

Oxford University Research Archive (ORA)

ORA - Oxford University Research Archive

Oxford University Research Archive

Oxford University Research Archive

ORA - Oxford University Research Archive