National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Protein Sci. 2020 Dec;29(12):2363-2374. doi: 10.1002/pro.3960. Epub 2020 Oct 15.
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.
人源 ABC 转运蛋白家族 B 亚家族成员 6（ABCB6）是一种 ABC 转运蛋白，参与转运有毒金属和抗癌药物。我们利用冷冻电镜技术，在非结合态下解析了全长 ABCB6 的分子结构。该结构揭示了全长 ABCB 转运蛋白的架构，其中包含两个 N 端跨膜结构域，这对于我们在体外实验中的 ATP 酶活性是必不可少的。ABCB6 的狭缝样底物结合口袋可能容纳卟啉的平面形状，而在线粒体膜间隙侧附近存在的二级腔将进一步促进底物释放。此外，用各种卟啉底物刺激的 ABCB6 的 ATP 酶活性在存在谷胱甘肽 (GSH) 时表现出不同的谱，表明存在依赖于 GSH 作为辅助因子的不同底物转运机制。
