Structural properties of model phosphatidylcholine flippases.
Lipid translocation from one lipid bilayer leaflet to the other, termed flip-flop, is required for the distribution of newly synthesized phospholipids during membrane biogenesis. However, a dedicated biogenic lipid flippase has not yet been identified. Here, we show that the efficiency by which model transmembrane peptides facilitate flip of reporter lipids with different headgroups critically depends on their content of helix-destabilizing residues, the charge state of polar flanking residues, and the composition of the host membrane. In particular, increased backbone dynamics of the transmembrane helix relates to its increased ability to flip lipids with phosphatidylcholine and phosphatidylserine headgroups, whereas a more rigid helix favors phosphatidylethanolamine flip. Further, the transmembrane domains of many SNARE protein subtypes share essential features with the dynamic model peptides. Indeed, recombinant SNAREs possess significant lipid flippase activity.
Lehrstuhl für Chemie der Biopolymere, Department für biowissenschaftliche Grundlagen, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising and Munich Center For Integrated Protein Science (CIPS(M)), Germany.
Marcella
M
Langer
Rashmi
R
Sah
Anika
A
Veser
Markus
M
Gütlich
Dieter
D
Langosch
D000595:Amino Acid Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D017433:Protein Structure, Secondary; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D010713:Phosphatidylcholines; D050600:SNARE Proteins