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

doi:10.1042/BST20190130

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

Pharmaceutical Sciences

Producción científica: Review article › revisión exhaustiva

59 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	1259-1268
Número de páginas	10
Publicación	Biochemical Society Transactions
Volumen	47
N.º	5
DOI	https://doi.org/10.1042/BST20190130
Estado	Published - oct 18 2019

Nota bibliográfica

Publisher Copyright:
© 2019 The Author(s).

Financiación

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.

Financiadores	Número del financiador
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

ODS de las Naciones Unidas

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Good health and well being

ASJC Scopus subject areas

Biochemistry

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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.",

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AU - Lee, Jyh Yeuan

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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