ABCG5/G8: A structural view to pathophysiology of the hepatobiliary cholesterol secretion

Aiman A. Zein, Rupinder Kaur, Toka O.K. Hussein, Gregory A. Graf, Jyh Yeuan Lee

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

Abstract

The ABCG5/G8 heterodimer is the primary neutral sterol transporter in hepatobiliary and transintestinal cholesterol excretion. Inactivating mutations on either the ABCG5 or ABCG8 subunit cause Sitosterolemia, a rare genetic disorder. In 2016, a crystal structure of human ABCG5/G8 in an apo state showed the first structural information on ATPbinding cassette (ABC) sterol transporters and revealed several structural features that were observed for the first time. Over the past decade, several missense variants of ABCG5/G8 have been associated with non-Sitosterolemia lipid phenotypes. In this review, we summarize recent pathophysiological and structural findings of ABCG5/G8, interpret the structure-function relationship in disease-causing variants and describe the available evidence that allows us to build a mechanistic view of ABCG5/G8-mediated sterol transport.

Original languageEnglish
Pages (from-to)1259-1268
Number of pages10
JournalBiochemical Society Transactions
Volume47
Issue number5
DOIs
StatePublished - Oct 18 2019

Bibliographical note

Funding Information:
We thank Ms. Molly de Barros, Ms. Chloé van de Panne and Dr. Bala Xavier for reading and commenting on the manuscript. This work was supported by a University of Ottawa Faculty of Medicine startup grant, a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) (RGPIN 2018-04070) and a National New Investigator Award from the Heart and Stroke Foundation of Canada to J.-Y.L., and by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK113625, R01DK100892), National Center for Research Resources (P20RR021954-05), the National Institute of General Medical Sciences (8P20GM103527), and the National Center for Advancing Translational Sciences (UL1TR000117) from the National Institutes of Health to G.A.G.

Publisher Copyright:
© 2019 The Author(s).

ASJC Scopus subject areas

  • Biochemistry

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