7E7I

Cryo-EM structure of human ABCA4 in the apo state

7E7I の概要

• エントリーDOI: 10.2210/pdb7e7i/pdb
• EMDBエントリー: 31000
• 分子名称: Retinal-specific phospholipid-transporting ATPase ABCA4, 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, ... (4 entities in total)
• 機能のキーワード: lipid transport, membrane protein, translocase
• 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: 266009.78

構造登録者

Xie, T.,Zhang, Z.K.,Gong, X. (登録日: 2021-02-26, 公開日: 2021-06-30, 最終更新日: 2025-07-02)

主引用文献

Xie, T.,Zhang, Z.,Fang, Q.,Du, B.,Gong, X.
Structural basis of substrate recognition and translocation by human ABCA4.
Nat Commun, 12:3853-3853, 2021

PubMed Abstract: Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3-3.4 Å. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport.

PubMed: 34158497
DOI: 10.1038/s41467-021-24194-6

実験手法

ELECTRON MICROSCOPY (3.3 Å)