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.

中文翻译：

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人ABCB6转运蛋白的冷冻电子显微镜结构

亚家族 B 的人类 ATP 结合盒转运蛋白 6 (ABCB6) 是一种 ABC 转运蛋白，参与易位有毒金属和抗癌药物。使用低温电子显微镜，我们确定了 apo 状态的全长 ABCB6 的分子结构。ABCB6 的结构揭示了全长 ABCB 转运蛋白的结构，该转运蛋白包含两个 N 端跨膜结构域，这对于我们的体外试验中的 ATP 酶活性是必不可少的。ABCB6 的狭缝状底物结合口袋可以容纳卟啉的平面形状，并且线粒体膜间隙侧附近的次级腔的存在将进一步促进底物释放。此外，在谷胱甘肽 (GSH) 存在下，ABCB6 的 ATPase 活性在各种卟啉底物刺激下表现出不同的特征，