5XJY

Cryo-EM structure of human ABCA1

Summary for 5XJY

• Entry DOI: 10.2210/pdb5xjy/pdb
• EMDB information: 6724
• Descriptor: 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)
• Functional Keywords: membrane transporter, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 261954.25

Authors

Qian, H.W.,Yan, N.,Gong, X. (deposition date: 2017-05-04, release date: 2017-06-07, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4.1 Å)