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 language | English |
|---|---|
| Pages (from-to) | 1259-1268 |
| Number of pages | 10 |
| Journal | Biochemical Society Transactions |
| Volume | 47 |
| Issue number | 5 |
| DOIs | |
| State | Published - Oct 18 2019 |
Bibliographical note
Publisher Copyright:© 2019 The Author(s).
Funding
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.
| Funders | Funder number |
|---|---|
| National Defense Medical Center Taiwan | |
| National Institutes of Health (NIH) | |
| National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences | 8P20GM103527 |
| National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences | |
| National Institute of Diabetes and Digestive and Kidney Diseases | R01DK100892, 1R01DK113625 |
| National Institute of Diabetes and Digestive and Kidney Diseases | |
| National Center for Research Resources | P20RR021954-05 |
| National Center for Research Resources | |
| National Center for Advancing Translational Sciences (NCATS) | UL1TR000117 |
| National Center for Advancing Translational Sciences (NCATS) | |
| Faculty of Health Sciences, University of Ottawa | |
| Natural Sciences and Engineering Research Council of Canada | RGPIN 2018-04070 |
| Natural Sciences and Engineering Research Council of Canada | |
| Heart and Stroke Foundation of Canada |
ASJC Scopus subject areas
- Biochemistry
