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Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A


Paulino, Cristina; Neldner, Yvonne; Lam, Andy Km; Kalienkova, Valeria; Brunner, Janine Denise; Schenck, Stephan; Dutzler, Raimund (2017). Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A. eLife, 6:26232.

Abstract

The calcium-activated chloride channel TMEM16A is a member of a conserved protein family that comprises ion channels and lipid scramblases. Although the structure of the scramblase nhTMEM16 has defined the architecture of the family, it was unknown how a channel has adapted to cope with its distinct functional properties. Here we have addressed this question by the structure determination of mouse TMEM16A by cryo-electron microscopy and a complementary functional characterization. The protein shows a similar organization to nhTMEM16, except for changes at the site of catalysis. There, the conformation of transmembrane helices constituting a membrane-spanning furrow that provides a path for lipids in scramblases has changed to form an enclosed aqueous pore that is largely shielded from the membrane. Our study thus reveals the structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the diverse functional behavior in the TMEM16 family.

Abstract

The calcium-activated chloride channel TMEM16A is a member of a conserved protein family that comprises ion channels and lipid scramblases. Although the structure of the scramblase nhTMEM16 has defined the architecture of the family, it was unknown how a channel has adapted to cope with its distinct functional properties. Here we have addressed this question by the structure determination of mouse TMEM16A by cryo-electron microscopy and a complementary functional characterization. The protein shows a similar organization to nhTMEM16, except for changes at the site of catalysis. There, the conformation of transmembrane helices constituting a membrane-spanning furrow that provides a path for lipids in scramblases has changed to form an enclosed aqueous pore that is largely shielded from the membrane. Our study thus reveals the structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the diverse functional behavior in the TMEM16 family.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:31 May 2017
Deposited On:08 Aug 2017 14:49
Last Modified:10 Aug 2017 07:51
Publisher:eLife Sciences Publications Ltd.
ISSN:2050-084X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/eLife.26232
PubMed ID:28561733

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Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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