Lopez Marques, Rosa Laura5; Poulsen, Lisbeth Rosager6; Bailly, Aurélien7; Geisler, Markus8; Günther-Pomorski, Thomas5; Palmgren, Michael Broberg5
1 Section for Transport Biology, Department of Plant and Environmental Sciences, Faculty of Science, Københavns Universitet2 Transport Biology, Department of Plant Biology, Faculty of Life Sciences, Københavns Universitet3 University of Zurich4 University of Fribourg5 Section for Transport Biology, Department of Plant and Environmental Sciences, Faculty of Science, Københavns Universitet6 Transport Biology, Department of Plant Biology, Faculty of Life Sciences, Københavns Universitet7 University of Zurich8 University of Fribourg
Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic molecules have also been found embedded in P-type ATPase crystal structures. Taken together, in two diverse groups of pumps, nature appears to have evolved quite similar ways of flipping phospholipids. General significance Our understanding of the structural basis for phospholipid flipping is still limited but it seems plausible that a general mechanism for phospholipid flipping exists in nature. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.
Biochimica Et Biophysica Acta - General Subjects, 2015, Vol 1850, Issue 3, p. 461-475
ABC transporter; Flippase; Lipid flipping; P-type ATPase; P4-ATPase; Transport