A flipping permease

Lipid bilayers should be a no-flipping zone for integral membrane proteins, with the hydrophobicity blocking any cross-membrane excursions. But now Mikhail Bogdanov, Phillip Heacock, and William Dowhan (University of Texas, Houston, TX) report that fully synthesized lactose permease (LacY) can reverse orientation when the lipid composition of the membrane is changed.

Dowhan focused on phosphatidylethanolamine (PE), which is the only zwitterionic lipid in Escherichia coli (the other lipids all have anionic head groups). He knew that PE was needed for LacY activity in vitro, and found that the same was true in vivo. Mutant E. coli lacking PE made a version of LacY that allowed facilitated but not active transport of lactose. This aberrant LacY had half of its 12 transmembrane domains in a configuration opposite to that of normal LacY. But when...