Structure and mechanism of ATP-dependent phospholipid transporters

TY - JOUR

T1 - Structure and mechanism of ATP-dependent phospholipid transporters

AU - Lopez Marques, Rosa Laura

AU - Poulsen, Lisbeth Rosager

AU - Bailly, Aurélien

AU - Geisler, Markus

AU - Günther-Pomorski, Thomas

AU - Palmgren, Michael Broberg

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - ABC transporter

KW - Flippase

KW - Lipid flipping

KW - P-type ATPase

KW - P4-ATPase

KW - Transport

U2 - 10.1016/j.bbagen.2014.04.008

DO - 10.1016/j.bbagen.2014.04.008

M3 - Journal article

C2 - 24746984

AN - SCOPUS:84921050654

SN - 0304-4165

VL - 1850

SP - 461

EP - 475

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

IS - 3

ER -