1. <scp>Cryo‐</scp> electron microscopy structure of human <scp>ABCB6</scp> transporter
- Author
-
Xiangxi Wang, Chunyu Wang, Can Cao, Xuejun C. Zhang, Xianping Wang, and Nan Wang
- Subjects
Porphyrins ,Mitochondrial intermembrane space ,Cryo-electron microscopy ,Full‐Length Papers ,ATP-binding cassette transporter ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Protein Domains ,Humans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,Cryoelectron Microscopy ,030302 biochemistry & molecular biology ,Substrate (chemistry) ,Transporter ,ABCB6 ,Glutathione ,Transmembrane domain ,HEK293 Cells ,chemistry ,biology.protein ,Biophysics ,ATP-Binding Cassette Transporters - Abstract
Human ATP‐binding cassette transporter 6 of subfamily B (ABCB6) is an ABC transporter involved in the translocation toxic metals and anti‐cancer drugs. Using cryo‐electron microscopy, we determined the molecular structure of full‐length ABCB6 in an apo state. The structure of ABCB6 unravels the architecture of a full‐length ABCB transporter that harbors two N‐terminal transmembrane domains which is indispensable for its ATPase activity in our in vitro assay. A slit‐like substrate binding pocket of ABCB6 may accommodate the planar shape of porphyrins, and the existence of a secondary cavity near the mitochondrial intermembrane space side would further facilitate substrate release. Furthermore, the ATPase activity of ABCB6 stimulated with a variety of porphyrin substrates showed different profiles in the presence of glutathione (GSH), suggesting the action of a distinct substrate translocation mechanism depending on the use of GSH as a cofactor.
- Published
- 2020
- Full Text
- View/download PDF