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Biochem Cell Biol. 2019 Jun;97(3):224-233. doi: 10.1139/bcb-2018-0151. Epub 2018 Jul 30.

Structural snapshot of the cholesterol-transport ATP-binding cassette proteins 1.

Author information

1
a Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
2
b Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Abstract

The ATP-binding cassette (ABC) proteins play critical roles in maintaining lipid and sterol homeostasis in higher eukaryotes. In humans, several subfamily-A and -G members function as cholesterol transporters across the cellular membranes. Deficiencies of these ABC proteins can cause dyslipidemia that is associated with health conditions such as atherosclerosis, diabetes, fatty liver disease, and neurodegeneration. The physiological roles of ABC cholesterol transporters have been implicated in mediating cholesterol efflux for reverse cholesterol transport and in maintaining membrane integrity for cell survival. The precise role of these ABC transporters in cells remains elusive, and little is known about the sterol-transport mechanism. The membrane constituents of ABC transporters have been postulated to play a key role in determining the transport substrates and the translocation mechanisms via the transmembrane domains. Recent breakthroughs in determining high-resolution structures of the human sterol transporter ABCG5/G8 and its functional homologs have shed light on new structural features of ABC transporters, providing a more relevant framework for mechanistic analysis of cholesterol-transport ABC proteins. This minireview outlines what is known about ABCG cholesterol transporters, addresses key structural features in the putative sterol translocation pathway on the transmembrane domains, and concludes by proposing a mechanistic model of ABC cholesterol transporters.

KEYWORDS:

ABCG transporter; ATP-binding cassette; cardiometabolic disease; cassette de liaison d’ATP; cholesterol efflux; domaine transmembranaire; maladie cardiométabolique; sortie de cholestérol; transmembrane domain; transporteur ABCG

PMID:
30058354
DOI:
10.1139/bcb-2018-0151
[Indexed for MEDLINE]

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