ABCG5/G8: a structural view to pathophysiology of the hepatobiliary cholesterol secretion. (18th October 2019)

• Record Type: Journal Article
• Authors: Zein, Aiman A.; Kaur, Rupinder; Hussein, Toka O.K.; Graf, Gregory A.; Lee, Jyh-Yeuan
• Is Part Of: Biochemical Society transactions. Volume 47:Number 5(2019)
• Page Start: 1259
• Page End: 1268
• Publication Date: 2019-10-18
• Subjects: ATP-binding cassette transporters -- cardiovascular disease -- cholesterol transport -- lipid metabolism -- sitosterolemia -- structural biology; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20190130
• Languages: English
• ISSNs: 0300-5127

Abstract

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.