5XJY

Cryo-EM structure of human ABCA1

5XJY の概要

• エントリーDOI: 10.2210/pdb5xjy/pdb
• EMDBエントリー: 6724
• 分子名称: ATP-binding cassette sub-family A member 1, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: membrane transporter, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 261954.25

構造登録者

Qian, H.W.,Yan, N.,Gong, X. (登録日: 2017-05-04, 公開日: 2017-06-07, 最終更新日: 2024-10-23)

主引用文献

Qian, H.,Zhao, X.,Cao, P.,Lei, J.,Yan, N.,Gong, X.
Structure of the Human Lipid Exporter ABCA1.
Cell, 169:1228-1239.e10, 2017

PubMed Abstract: 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.

PubMed: 28602350
DOI: 10.1016/j.cell.2017.05.020

実験手法

ELECTRON MICROSCOPY (4.1 Å)