Allosteric coupling between proximal C-terminus and selectivity filter is facilitated by the movement of transmembrane segment 4 in TREK-2 channel

Scientific Reports
Ren-Gong ZhuoXiao-Yun Ma

Abstract

TREK-2, a member of two-pore-domain potassium channel family, regulates cellular excitability in response to diverse stimuli. However, how such stimuli control channel function remains unclear. Here, by characterizing the responses of cytosolic proximal C-terminus deletant (ΔpCt) and transmembrane segment 4 (M4)-glycine hinge mutant (G312A) to 2-Aminoethoxydiphenyl borate (2-APB), an activator of TREK-2, we show that the transduction initiated from pCt domain is allosterically coupled with the conformation of selectivity filter (SF) via the movements of M4, without depending on the original status of SF. Moreover, ΔpCt and G312A also exhibited blunted responses to extracellular alkalization, a model to induce SF conformational transition. These results suggest that the coupling between pCt domain and SF is bidirectional, and M4 movements are involved in both processes. Further mechanistic exploration reveals that the function of Phe316, a residue close to the C-terminus of M4, is associated with such communications. However, unlike TREK-2, M4-hinge of TREK-1 only controls the transmission from pCt to SF, rather than SF conformational changes triggered by pHo changes. Together, our findings uncover the unique gating properties o...Continue Reading

References

Apr 5, 2000·The Journal of Biological Chemistry·H BangD Kim
May 31, 2002·Nature·Youxing JiangRoderick MacKinnon
Oct 20, 2004·Biochemistry·Elhanan Magidovich, Ofer Yifrach
Nov 20, 2004·Nature Reviews. Neuroscience·Kenton J Swartz
Aug 19, 2007·Neuron·Markus RapediusThomas Baukrowitz
Apr 18, 2008·The Journal of Biological Chemistry·Catherine E ClarkeAlistair Mathie
Dec 23, 2008·Nature Structural & Molecular Biology·Yuval Ben-AbuOfer Yifrach
Apr 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Serdar UysalAnthony Kossiakoff
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Guillaume SandozFlorian Lesage
Mar 31, 2010·The Journal of Biological Chemistry·María Isabel NiemeyerFrancisco V Sepúlveda
Apr 16, 2010·Physiological Reviews·Péter Enyedi, Gábor Czirják
Aug 9, 2011·The EMBO Journal·Paula L PiechottaThomas Baukrowitz
Jan 11, 2012·Nature Structural & Molecular Biology·Vassiliy N BavroStephen J Tucker
Jan 28, 2012·Science·Alexandria N Miller, Stephen B Long
Jun 26, 2012·The EMBO Journal·Sviatoslav N BagriantsevDaniel L Minor
Sep 21, 2012·Frontiers in Pharmacology·Alain J Labro, Dirk J Snyders
Sep 29, 2012·The Journal of Biological Chemistry·Élise FaureRikard Blunck
Mar 26, 2013·The Journal of Biological Chemistry·Michael C Puljung, William N Zagotta
Sep 21, 2013·Nature Communications·Claire BagnérisB A Wallace
Jan 11, 2014·Pflügers Archiv : European journal of physiology·Christina M HullTom W Claydon
Jan 24, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristian AcostaSally N Lawson
Mar 14, 2014·Biochemistry·Raymond E HulseEduardo Perozo
May 16, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zhaoyang XiaoSaobo Lei
Jul 9, 2014·Nature Communications·Prafulla AryalStephen J Tucker
Dec 5, 2014·Nature·Stephen G BrohawnRoderick MacKinnon

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Citations

Apr 6, 2017·Scientific Reports·Matthew P HarriganVijay S Pande
Nov 23, 2017·ELife·Luis G CuelloEduardo Perozo
Jun 9, 2016·Molecular Pharmacology·María Isabel NiemeyerFrancisco V Sepúlveda
Jul 21, 2017·Channels·Ehsan Nematian-ArdestaniStephen J Tucker
Sep 21, 2018·Frontiers in Molecular Neuroscience·Ismail Ben SoussiaFlorian Lesage
May 28, 2019·Chemical Biology & Drug Design·Daniel Şterbuleac
Oct 24, 2020·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Sung Eun KimSung Joon Kim
Dec 22, 2020·ELife·Aboubacar WaguePaul M Riegelhaupt
Jul 18, 2020·Annual Review of Pharmacology and Toxicology·Alistair MathiePaul D Wright
Apr 23, 2021·Journal of Molecular Biology·Andrew M NataleDaniel L Minor

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Methods Mentioned

BETA
PCR
in vitro transcription

Software Mentioned

GraphPad prism
GraphPad
Clampex

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