Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel

Summary: Recently identified proton-activated chloride channel (PAC) contains two transmembrane helices (S1–S2) and is involved in lysosome function, hypoxia adaption, stroke, and carcinogenesis. Although a PAC structure was recently resolved, its gating and activation mechanisms remained largely un...

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Autores principales:	Ruiqi Cai, Jingfeng Tang, Xing-Zhen Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Cell biology Structural biology Science Q
Acceso en línea:	https://doaj.org/article/5c86f1ba1d6a42279bbb7b9ae880bb71
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spelling	oai:doaj.org-article:5c86f1ba1d6a42279bbb7b9ae880bb712021-11-16T04:11:02ZIon permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel2589-004210.1016/j.isci.2021.103395https://doaj.org/article/5c86f1ba1d6a42279bbb7b9ae880bb712021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013663https://doaj.org/toc/2589-0042Summary: Recently identified proton-activated chloride channel (PAC) contains two transmembrane helices (S1–S2) and is involved in lysosome function, hypoxia adaption, stroke, and carcinogenesis. Although a PAC structure was recently resolved, its gating and activation mechanisms remained largely unknown. By the two-electrode voltage clamp electrophysiology in Xenopus oocytes, we found that the hydrophobicity of site 304 at fenestrations, but not that of neighbor sites, is important for maintaining PAC at a closed state at pH 7.5. When activated at acidic pH, PAC activity significantly increased with the hydrophilicity of site 307 within S2, but not with that of neighbor sites, suggesting that 307 acts as an activation gate. We identified six conserved protonatable residues critical for proton-induced activation, consistent with structural studies. Our study depicted a scheme in which proton binding induces conformational changes from the W304-controlled closed state at fenestrations to an activated state controlled by activation gate I307 in helix S2.Ruiqi CaiJingfeng TangXing-Zhen ChenElsevierarticleMolecular biologyCell biologyStructural biologyScienceQENiScience, Vol 24, Iss 12, Pp 103395- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Cell biology Structural biology Science Q
spellingShingle	Molecular biology Cell biology Structural biology Science Q Ruiqi Cai Jingfeng Tang Xing-Zhen Chen Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
description	Summary: Recently identified proton-activated chloride channel (PAC) contains two transmembrane helices (S1–S2) and is involved in lysosome function, hypoxia adaption, stroke, and carcinogenesis. Although a PAC structure was recently resolved, its gating and activation mechanisms remained largely unknown. By the two-electrode voltage clamp electrophysiology in Xenopus oocytes, we found that the hydrophobicity of site 304 at fenestrations, but not that of neighbor sites, is important for maintaining PAC at a closed state at pH 7.5. When activated at acidic pH, PAC activity significantly increased with the hydrophilicity of site 307 within S2, but not with that of neighbor sites, suggesting that 307 acts as an activation gate. We identified six conserved protonatable residues critical for proton-induced activation, consistent with structural studies. Our study depicted a scheme in which proton binding induces conformational changes from the W304-controlled closed state at fenestrations to an activated state controlled by activation gate I307 in helix S2.
format	article
author	Ruiqi Cai Jingfeng Tang Xing-Zhen Chen
author_facet	Ruiqi Cai Jingfeng Tang Xing-Zhen Chen
author_sort	Ruiqi Cai
title	Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
title_short	Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
title_full	Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
title_fullStr	Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
title_full_unstemmed	Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
title_sort	ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5c86f1ba1d6a42279bbb7b9ae880bb71
work_keys_str_mv	AT ruiqicai ionpermeationcontrolledbyhydrophobicresiduesandprotonbindingintheprotonactivatedchloridechannel AT jingfengtang ionpermeationcontrolledbyhydrophobicresiduesandprotonbindingintheprotonactivatedchloridechannel AT xingzhenchen ionpermeationcontrolledbyhydrophobicresiduesandprotonbindingintheprotonactivatedchloridechannel
_version_	1718426725714493440

Ion permeation controlled by hydrophobic residues and proton binding in the proton-activated chloride channel

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