Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, U.S.A.
Biochem Soc Trans. 2019 Oct 31;47(5):1259-1268. doi: 10.1042/BST20190130.
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.
ABCG5/G8 异二聚体是肝胆和肠内胆固醇排泄的主要中性固醇转运蛋白。ABCG5 或 ABCG8 亚基的失活突变导致甾醇血症，这是一种罕见的遗传疾病。2016 年，apo 状态下的人 ABCG5/G8 晶体结构显示了 ATP 结合盒 (ABC) 固醇转运蛋白的首个结构信息，并揭示了首次观察到的几个结构特征。在过去的十年中，几种 ABCG5/G8 的错义变体与非甾醇血症脂质表型有关。在这篇综述中，我们总结了 ABCG5/G8 的最新病理生理学和结构发现，解释了致病变体中的结构-功能关系，并描述了可用的证据，使我们能够建立 ABCG5/G8 介导的固醇转运的机制观点。
