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-Structure paper
Title | Molecular insights into the human ABCB6 transporter. |
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Journal, issue, pages | Cell Discov, Vol. 7, Issue 1, Page 55, Year 2021 |
Publish date | Jul 27, 2021 |
Authors | Guangyuan Song / Sensen Zhang / Mengqi Tian / Laixing Zhang / Runyu Guo / Wei Zhuo / Maojun Yang / |
PubMed Abstract | ABCB6 plays a crucial role in energy-dependent porphyrin transport, drug resistance, toxic metal resistance, porphyrin biosynthesis, protection against stress, and encoding a blood group system ...ABCB6 plays a crucial role in energy-dependent porphyrin transport, drug resistance, toxic metal resistance, porphyrin biosynthesis, protection against stress, and encoding a blood group system Langereis antigen. However, the mechanism underlying porphyrin transport is still unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structures of nanodisc-reconstituted human ABCB6 trapped in an apo-state and an ATP-bound state at resolutions of 3.6 and 3.5 Å, respectively. Our structures reveal a unique loop in the transmembrane domain (TMD) of ABCB6, which divides the TMD into two cavities. It restrains the access of substrates in the inward-facing state and is removed by ATP-driven conformational change. No ligand cavities were observed in the nucleotide-bound state, indicating a state following substrate release but prior to ATP hydrolysis. Structural analyses and functional characterizations suggest an "ATP-switch" model and further reveal the conformational changes of the substrate-binding pockets triggered by the ATP-driven regulation. |
External links | Cell Discov / PubMed:34312373 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 - 3.6 Å |
Structure data | EMDB-31169, PDB-7ekl: EMDB-31170, PDB-7ekm: |
Chemicals | ChemComp-ATP: ChemComp-MG: |
Source |
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Keywords | MEMBRANE PROTEIN / mitochondrial outer membrane protein |