7E7O
Cryo-EM structure of human ABCA4 in NRPE-bound state
Summary for 7E7O
| Entry DOI | 10.2210/pdb7e7o/pdb |
| EMDB information | 31000 31001 |
| Descriptor | 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, ... (5 entities in total) |
| Functional Keywords | lipid transport, membrane protein, translocase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 267768.30 |
| Authors | Xie, T.,Zhang, Z.K.,Gong, X. (deposition date: 2021-02-26, release date: 2021-06-30, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 34158497DOI: 10.1038/s41467-021-24194-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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