Details
- Autor(en) / Beteiligte
- Titel
- Crystal structure of the human sterol transporter ABCG5/ABCG8
- Ist Teil von
- Nature (London), 2016-05, Vol.533 (7604), p.561-564
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Beschreibungen/Notizen
- ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Here we use crystallization in lipid bilayers to determine the X-ray structure of human G5G8 in a nucleotide-free state at 3.9 Å resolution, generating the first atomic model of an ABC sterol transporter. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. The G5G8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolaemia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature17666Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4964963
- Format
- –
- Schlagworte
- ABC transporters, Adenosine Triphosphatases - metabolism, Amino Acid Sequence, Atherosclerosis, ATP Binding Cassette Transporter, Subfamily G, Member 5, ATP Binding Cassette Transporter, Subfamily G, Member 8, ATP-Binding Cassette Transporters - chemistry, ATP-Binding Cassette Transporters - genetics, ATP-Binding Cassette Transporters - metabolism, BASIC BIOLOGICAL SCIENCES, Binding Sites, Biocatalysis, Carrier proteins, Cholesterol, Crystal structure, Crystallography, X-Ray, Crystals, Humans, Hypercholesterolemia - genetics, Intestinal Diseases - genetics, Lipid Bilayers - chemistry, Lipid Bilayers - metabolism, Lipid Metabolism, Inborn Errors - genetics, Lipids, Lipoproteins - chemistry, Lipoproteins - genetics, Lipoproteins - metabolism, Membranes, Models, Molecular, Molecular Sequence Data, Mutation, Nucleotides, Observations, Physiological aspects, Phytosterols - adverse effects, Phytosterols - genetics, Polypeptides, Protein Folding, Protein Multimerization, Protein Structure, Tertiary, Sterols, Sterols - metabolism, Structure, Transporters, X-ray crystallography