7LKZ

Structure of ATP-bound human ABCA4

Summary for 7LKZ

• Entry DOI: 10.2210/pdb7lkz/pdb
• EMDB information: 23410
• Descriptor: Retinal-specific phospholipid-transporting ATPase ABCA4, beta-D-mannopyranose-(1-4)-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, ... (8 entities in total)
• Functional Keywords: abc transporter, importer, membrane protein, translocase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 266042.52

Authors

Liu, F.,Lee, J.,Chen, J. (deposition date: 2021-02-03, release date: 2021-03-03, Last modification date: 2024-10-23)

Primary citation

Liu, F.,Lee, J.,Chen, J.
Molecular structures of the eukaryotic retinal importer ABCA4.
Elife, 10:-, 2021

PubMed Abstract: The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here, we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids.

PubMed: 33605212
DOI: 10.7554/eLife.63524

Experimental method

ELECTRON MICROSCOPY (3.27 Å)