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| Title | Structure of the human lipid exporter ABCB4 in a lipid environment. |
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| Journal, issue, pages | Nat Struct Mol Biol, Vol. 27, Issue 1, Page 62-70, Year 2020 |
| Publish date | Dec 23, 2019 |
 Authors | Jeppe A Olsen / Amer Alam / Julia Kowal / Bruno Stieger / Kaspar P Locher /   |
| 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 ...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. |
 External links | Nat Struct Mol Biol / PubMed:31873305 |
| Methods | EM (single particle) |
| Resolution | 3.2 Å |
| Structure data | EMDB-10111, PDB-6s7p: |
| Chemicals |  ChemComp-ATP:  ChemComp-MG:  ChemComp-CLR: |
| Source |
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 Keywords | TRANSPORT PROTEIN / ABC Transporter / Lipid extruder |
homo sapiens (human)