TY - JOUR

T1 - Reconstitution of ATP-dependent lipid transporters

T2 - gaining insight into molecular characteristics, regulation, and mechanisms

AU - Herrera, Sara Abad

AU - Pomorski, Thomas Günther

N1 - Publisher Copyright: © 2023 The Author(s).

PY - 2023

Y1 - 2023

N2 - Lipid transporters play a crucial role in supporting essential cellular processes such as organelle assembly, vesicular trafficking, and lipid homeostasis by driving lipid transport across membranes. Cryo-electron microscopy has recently resolved the structures of several ATP-dependent lipid transporters, but functional characterization remains a major challenge. Although studies of detergent-purified proteins have advanced our understanding of these transporters, in vitro evidence for lipid transport is still limited to a few ATP-dependent lipid transporters. Reconstitution into model membranes, such as liposomes, is a suitable approach to study lipid transporters in vitro and to investigate their key molecular features. In this review, we discuss the current approaches for reconstituting ATP-driven lipid transporters into large liposomes and common techniques used to study lipid transport in proteoliposomes. We also highlight the existing knowledge on the regulatory mechanisms that modulate the activity of lipid transporters, and finally, we address the limitations of the current approaches and future perspectives in this field.

AB - Lipid transporters play a crucial role in supporting essential cellular processes such as organelle assembly, vesicular trafficking, and lipid homeostasis by driving lipid transport across membranes. Cryo-electron microscopy has recently resolved the structures of several ATP-dependent lipid transporters, but functional characterization remains a major challenge. Although studies of detergent-purified proteins have advanced our understanding of these transporters, in vitro evidence for lipid transport is still limited to a few ATP-dependent lipid transporters. Reconstitution into model membranes, such as liposomes, is a suitable approach to study lipid transporters in vitro and to investigate their key molecular features. In this review, we discuss the current approaches for reconstituting ATP-driven lipid transporters into large liposomes and common techniques used to study lipid transport in proteoliposomes. We also highlight the existing knowledge on the regulatory mechanisms that modulate the activity of lipid transporters, and finally, we address the limitations of the current approaches and future perspectives in this field.

KW - ABC transporter

KW - Flipppase

KW - Liposomes

KW - P-type ATPase

KW - Reconstitution

U2 - 10.1042/BSR20221268

DO - 10.1042/BSR20221268

M3 - Review

C2 - 37417269

AN - SCOPUS:85167480776

VL - 43

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 8

ER -