@article{b273e5625fb64edf85c75049913dffec,
title = "Crystal structure of the human sterol transporter ABCG5/ABCG8",
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 {\AA} 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.",
author = "Lee, {Jyh Yeuan} and Kinch, {Lisa N.} and Borek, {Dominika M.} and Jin Wang and Junmei Wang and Urbatsch, {Ina L.} and Xie, {Xiao Song} and Grishin, {Nikolai V.} and Cohen, {Jonathan C.} and Zbyszek Otwinowski and Hobbs, {Helen H.} and Rosenbaum, {Daniel M.}",
note = "Funding Information: We thank the University of Texas Southwestern Structural Biology Laboratory and the staff of the Advanced Photon Source (beamlines 19ID and 23ID) for support during data collection. We thank C. Zelasko, L. Donnelly, F. Xu, L. Nie, Z. Wang, Y. Ma, and C. Zhao for technical assistance. We also thank S. Wilkens for comments, and L. Rice, Y. Jiang, and R. Hibbs for providing reagents and equipment. This project was supported by grants from the American Heart Association South Central Affiliate-(0825285F; J.-Y.L.), the American Heart Association Texas Affiliate Beginning Grant-in-Aid (0463130Y; I.L.U.), the Welch Foundation (I-1770; D.M.R.), the Packard Foundation (D.M.R.), the Howard Hughes Medical Institute (H.H.H., N.V.G.), and the National Institutes of Health (HL72304 and P01-HL20948 (H.H.H., J.C.C., X.-S.X.), GM094575 (N.V.G.), GM053163 and GM117080 (Z.O.), and GM113050 (D.M.R.)). The Advanced Photon Source is a US Department of Energy Office of Science User Facility operated for the Department of Energy Office of Science by Argonne National Laboratory (DE-AC02-06CH11357).",
year = "2016",
month = may,
day = "4",
doi = "10.1038/nature17666",
language = "English (US)",
volume = "533",
pages = "561--564",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7604",
}