2015CB910101, 2016YFA0500402, 2014ZX09507003-006 and 2016YFA0501100
中国
the National Natural Science Foundation of China
31621092, 31630017, and 31611130036
中国
引用
ジャーナル: Cell / 年: 2017 タイトル: Structure of the Human Lipid Exporter ABCA1. 著者: Hongwu Qian / Xin Zhao / Pingping Cao / Jianlin Lei / Nieng Yan / Xin Gong / 要旨: ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of ...ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL deficiency. Here, we report the cryo-EM structure of human ABCA1 with nominal resolutions of 4.1 Å for the overall structure and 3.9 Å for the massive extracellular domain. The nucleotide-binding domains (NBDs) display a nucleotide-free state, while the two transmembrane domains (TMDs) contact each other through a narrow interface in the intracellular leaflet of the membrane. In addition to TMDs and NBDs, two extracellular domains of ABCA1 enclose an elongated hydrophobic tunnel. Structural mapping of dozens of disease-related mutations allows potential interpretation of their diverse pathogenic mechanisms. Structural-based analysis suggests a plausible "lateral access" mechanism for ABCA1-mediated lipid export that may be distinct from the conventional alternating-access paradigm.
EMPIAR-10798 (タイトル: Cryo-EM micrographs of human ABCA1 / Data size: 16.3 TB Data #1: The micrographs are the movie stacks (32 frames) after motion corrected with MotionCorr and binned 2-fold, resulting in a pixel size of 1.307 Å/pixel. [micrographs - multiframe])