7TBZ

The structure of ABCA1 Y482C

Summary for 7TBZ

• Entry DOI: 10.2210/pdb7tbz/pdb
• EMDB information: 25800 25801 25802 25803
• Descriptor: ATP-binding cassette, sub-family A (ABC1), member 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (5 entities in total)
• Functional Keywords: hdl, cholesterol, tangier disease, abc transporter, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 257759.25

Authors

Sun, Y.,Li, X. (deposition date: 2021-12-22, release date: 2022-01-26, Last modification date: 2024-10-16)

Primary citation

Sun, Y.,Li, X.
Cholesterol efflux mechanism revealed by structural analysis of human ABCA1 conformational states.
Nat Cardiovasc Res, 1:238-245, 2022

PubMed Abstract: ATP-binding cassette transporter A1 (ABCA1) utilizes energy derived from ATP hydrolysis to export cholesterol and phospholipids from macrophages. ABCA1 plays a central role in the biosynthesis of high-density lipoprotein (HDL), which mediates reverse cholesterol transport and prevents detrimental lipid deposition. Mutations in ABCA1 cause Tangier disease characterized by a remarkable reduction in the amount of HDL in blood. Here we present cryo-electron microscopy structures of human ABCA1 in ATP-bound and nucleotide-free states. Structural comparison reveals that ATP molecules pull the nucleotide-binding domains together, inducing movements of transmembrane helices 1, 2, 7 and 8 through a series of salt-bridge interactions. Subsequently, extracellular domains (ECDs) undergo a rotation and introduce conformational changes in the ECD-transmembrane interface. In addition, while we observe a sterol-like molecule in ECDs, no such density was observed in the structure of an HDL-deficiency mutant ABCA1, demonstrating the physiological importance of ECDs and a putative interaction mode between ABCA1 and its lipid acceptors. Thus, these structures, along with cholesterol efflux assays, advance the understanding ABCA1-mediated reverse cholesterol transport.

PubMed: 37181814
DOI: 10.1038/s44161-022-00022-y

Experimental method

ELECTRON MICROSCOPY (4.3 Å)