| http://purl.uniprot.org/citations/33228147 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33228147 | http://www.w3.org/2000/01/rdf-schema#comment | "The heterodimeric ATP-binding cassette (ABC) sterol transporter, ABCG5/G8, is responsible for the biliary and transintestinal secretion of cholesterol and dietary plant sterols. Missense mutations of ABCG5/G8 can cause sitosterolemia, a loss-of-function disorder characterized by plant sterol accumulation and premature atherosclerosis. A new molecular framework was recently established by a crystal structure of human ABCG5/G8 and reveals a network of polar and charged amino acids in the core of the transmembrane domains, namely, a polar relay. In this study, we utilize genetic variants to dissect the mechanistic role of this transmembrane polar relay in controlling ABCG5/G8 function. We demonstrated a sterol-coupled ATPase activity of ABCG5/G8 by cholesteryl hemisuccinate (CHS), a relatively water-soluble cholesterol memetic, and characterized CHS-coupled ATPase activity of three loss-of-function missense variants, R543S, E146Q, and A540F, which are respectively within, in contact with, and distant from the polar relay. The results established an in vitro phenotype of the loss-of-function and missense mutations of ABCG5/G8, showing significantly impaired ATPase activity and loss of energy sufficient to weaken the signal transmission from the transmembrane domains. Our data provide a biochemical evidence underlying the importance of the polar relay and its network in regulating the catalytic activity of ABCG5/G8 sterol transporter."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.org/dc/terms/identifier | "doi:10.3390/ijms21228747"xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/author | "Lee J.Y."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/author | "Xavier B.M."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/author | "Venes A."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/author | "Zein A.A."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/name | "Int J Mol Sci"xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/pages | "E8747"xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/title | "Transmembrane Polar Relay Drives the Allosteric Regulation for ABCG5/G8 Sterol Transporter."xsd:string |
| http://purl.uniprot.org/citations/33228147 | http://purl.uniprot.org/core/volume | "21"xsd:string |
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