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

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 ATP-binding 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.

• Authors: Aiman A Zein, Rupinder Kaur, Toka O K Hussein, Gregory A Graf, Jyh-Yeuan Lee
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 47 Issue 5 Pg. 1259-1268 (10 31 2019) ISSN: 1470-8752 [Electronic] England
• PMID: 31654053 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2019 The Author(s).

Chemical References

• ABCG5 protein, human
• ABCG8 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 5
• ATP Binding Cassette Transporter, Subfamily G, Member 8
• Lipoproteins
• Phytosterols
• Cholesterol

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 5 (biosynthesis, chemistry, metabolism)
• ATP Binding Cassette Transporter, Subfamily G, Member 8 (biosynthesis, chemistry, metabolism)
• Animals
• Biliary Tract (metabolism)
• Catalysis
• Cholesterol (metabolism)
• Homeostasis
• Humans
• Hypercholesterolemia (metabolism)
• Intestinal Diseases (metabolism)
• Lipid Metabolism, Inborn Errors (metabolism)
• Lipoproteins (biosynthesis, chemistry, metabolism)
• Liver (metabolism)
• Phytosterols (adverse effects, metabolism)