5DO7

Crystal Structure of the Human Sterol Transporter ABCG5/ABCG8

Summary for 5DO7

• Entry DOI: 10.2210/pdb5do7/pdb
• Descriptor: ATP-binding cassette sub-family G member 5, ATP-binding cassette sub-family G member 8 (2 entities in total)
• Functional Keywords: atp-binding cassette transporter, abcg, sterol efflux, sitosterolemia, transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 302990.58

Authors

Lee, J.-Y.,Kinch, L.N.,Borek, D.M.,Urbatsch, I.L.,Xie, X.-S.,Grishin, N.V.,Cohen, J.C.,Otwinowski, Z.,Hobbs, H.H.,Rosenbaum, D.M. (deposition date: 2015-09-10, release date: 2016-05-11, Last modification date: 2024-03-06)

Primary citation

Lee, J.Y.,Kinch, L.N.,Borek, D.M.,Wang, J.,Wang, J.,Urbatsch, I.L.,Xie, X.S.,Grishin, N.V.,Cohen, J.C.,Otwinowski, Z.,Hobbs, H.H.,Rosenbaum, D.M.
Crystal structure of the human sterol transporter ABCG5/ABCG8.
Nature, 533:561-564, 2016

PubMed Abstract: 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.

PubMed: 27144356
DOI: 10.1038/nature17666

Experimental method

X-RAY DIFFRACTION (3.93 Å)