10.5061/DRYAD.69P8CZ92N
Sukalskaia, Anastasiia
0000-0001-8096-2741
University of Zurich
Dutzler, Raimund
University of Zurich
A liposome assay showing the absence of scrambling in TTYH proteins and a
lipidomics analysis of TTYH2
Dryad
dataset
2021
2021-07-27T00:00:00Z
2021-07-27T00:00:00Z
en
61139870 bytes
9
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
The Tweety homologues (TTYHs) are members of a conserved family of
eukaryotic membrane proteins that are abundant in the brain. The three
human paralogs were assigned to function as anion channels that are either
activated by Ca2+ or cell swelling. To uncover their unknown architecture
and its relationship to function, we have determined the structures of
human TTYH1–3 by cryo-electron microscopy. All structures display
equivalent features of a dimeric membrane protein that contains five
transmembrane segments and an extended extracellular domain. As none of
the proteins shows features reminiscent of an anion channel, we revisited
functional experiments and did not find any indication of ion conduction.
Instead, we find density in an extended hydrophobic pocket contained in
the extracellular domain that emerges from the lipid bilayer, which
suggests a role of TTYH proteins in the interaction with lipid-like
compounds residing in the membrane.