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Structural basis for phospholipid scrambling in the TMEM16 family


Brunner, Janine D; Schenck, Stephan; Dutzler, Raimund (2016). Structural basis for phospholipid scrambling in the TMEM16 family. Current Opinion in Structural Biology, 39:61-70.

Abstract

Upon activation, lipid scramblases dissipate the lipid asymmetry of membranes, in an ATP-independent manner, by catalyzing flip-flop of lipids between the leaflets. The molecular identities of these proteins long remained obscure, but in recent years the TMEM16 family of proteins has been found to constitute Ca(2+)-activated scramblases. Recently, the X-ray structure of a fungal TMEM16 homologue has provided insight into the architecture of this protein family and into potential scrambling mechanisms. The protein forms homodimers with each subunit containing a membrane-spanning hydrophilic cleft. This region is of sufficient size to harbor polar headgroups on their way across the membrane and thus may lower the energetic barrier for the diffusion of lipids between the two leaflets of the bilayer. A regulatory Ca(2+) binding site located within the membrane adjacent to this hydrophobic cleft is responsible for activation by yet unknown mechanisms.

Abstract

Upon activation, lipid scramblases dissipate the lipid asymmetry of membranes, in an ATP-independent manner, by catalyzing flip-flop of lipids between the leaflets. The molecular identities of these proteins long remained obscure, but in recent years the TMEM16 family of proteins has been found to constitute Ca(2+)-activated scramblases. Recently, the X-ray structure of a fungal TMEM16 homologue has provided insight into the architecture of this protein family and into potential scrambling mechanisms. The protein forms homodimers with each subunit containing a membrane-spanning hydrophilic cleft. This region is of sufficient size to harbor polar headgroups on their way across the membrane and thus may lower the energetic barrier for the diffusion of lipids between the two leaflets of the bilayer. A regulatory Ca(2+) binding site located within the membrane adjacent to this hydrophobic cleft is responsible for activation by yet unknown mechanisms.

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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:10 June 2016
Deposited On:28 Jul 2016 12:11
Last Modified:29 Jul 2016 07:57
Publisher:Elsevier
ISSN:0959-440X
Publisher DOI:https://doi.org/10.1016/j.sbi.2016.05.020
PubMed ID:27295354

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