6S7P
Nucleotide bound ABCB4
Summary for 6S7P
| Entry DOI | 10.2210/pdb6s7p/pdb |
| EMDB information | 10111 |
| Descriptor | Phosphatidylcholine translocator ABCB4, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | abc transporter, lipid extruder, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 144965.30 |
| Authors | Olsen, J.A.,Alam, A.,Kowal, J.,Stieger, B.,Locher, K.P. (deposition date: 2019-07-05, release date: 2019-12-25, Last modification date: 2024-05-22) |
| Primary citation | Olsen, J.A.,Alam, A.,Kowal, J.,Stieger, B.,Locher, K.P. Structure of the human lipid exporter ABCB4 in a lipid environment. Nat.Struct.Mol.Biol., 27:62-70, 2020 Cited by PubMed Abstract: ABCB4 is an ATP-binding cassette transporter that extrudes phosphatidylcholine into the bile canaliculi of the liver. Its dysfunction or inhibition by drugs can cause severe, chronic liver disease or drug-induced liver injury. We determined the cryo-EM structure of nanodisc-reconstituted human ABCB4 trapped in an ATP-bound state at a resolution of 3.2 Å. The nucleotide binding domains form a closed conformation containing two bound ATP molecules, but only one of the ATPase sites contains bound Mg. The transmembrane domains adopt a collapsed conformation at the level of the lipid bilayer, but we observed a large, hydrophilic and fully occluded cavity at the level of the cytoplasmic membrane boundary, with no ligand bound. This indicates a state following substrate release but prior to ATP hydrolysis. Our results rationalize disease-causing mutations in human ABCB4 and suggest an 'alternating access' mechanism of lipid extrusion, distinct from the 'credit card swipe' model of other lipid transporters. PubMed: 31873305DOI: 10.1038/s41594-019-0354-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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