Structural basis for phospholipid scrambling in the TMEM16 family.

TitleStructural basis for phospholipid scrambling in the TMEM16 family.
Publication TypeJournal Article
Year of Publication2016
AuthorsBrunner, J. D., S. Schenck, and R. Dutzler
JournalCurr Opin Struct Biol
Volume39
Pagination61-70
Date Published2016 08
ISSN1879-033X
KeywordsAmino Acid Sequence, Animals, Anoctamins, Calcium, Humans, Hydrophobic and Hydrophilic Interactions, Phospholipids
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-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 binding site located within the membrane adjacent to this hydrophobic cleft is responsible for activation by yet unknown mechanisms.

DOI10.1016/j.sbi.2016.05.020
Alternate JournalCurr. Opin. Struct. Biol.
PubMed ID27295354
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