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Publication Abstract from PubMed

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 A, 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.

Molecular insights into the human ABCB6 transporter.,Song G, Zhang S, Tian M, Zhang L, Guo R, Zhuo W, Yang M Cell Discov. 2021 Jul 27;7(1):55. doi: 10.1038/s41421-021-00284-z. PMID:34312373^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.