Wuxi Biortus Biosciences Co. Ltd., 6 Dongsheng Western Road, 214437, Jiangyin, Jiangsu, China.
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, 430030, Wuhan, Hubei Province, China.
Nat Commun. 2023 Apr 11;14(1):2030. doi: 10.1038/s41467-023-37851-9.
ABCB10, a member of ABC transporter superfamily that locates in the inner membrane of mitochondria, plays crucial roles in hemoglobin synthesis, antioxidative stress and stabilization of the iron transporter mitoferrin-1. Recently, it was found that ABCB10 is a mitochondrial biliverdin exporter. However, the molecular mechanism of biliverdin export by ABCB10 remains elusive. Here we report the cryo-EM structures of ABCB10 in apo (ABCB10-apo) and biliverdin-bound form (ABCB10-BV) at 3.67 Å and 2.85 Å resolution, respectively. ABCB10-apo adopts a wide-open conformation and may thus represent the apo form structure. ABCB10-BV forms a closed conformation and biliverdin situates in a hydrophobic pocket in one protomer and bridges the interaction through hydrogen bonds with the opposing one. We also identify cholesterols sandwiched by BVs and discuss the export dynamics based on these structural and biochemical observations.
ABCB10 是 ABC 转运蛋白超家族的成员，位于线粒体的内膜，在血红蛋白合成、抗氧化应激和铁转运蛋白 mitoferrin-1 的稳定中发挥关键作用。最近，发现 ABCB10 是一种线粒体胆绿素外排泵。然而，ABCB10 胆绿素外排的分子机制仍不清楚。在这里，我们报道了 ABCB10 在apo（ABCB10-apo）和胆绿素结合形式（ABCB10-BV）下的 cryo-EM 结构，分辨率分别为 3.67Å 和 2.85Å。ABCB10-apo 采用大开合构象，因此可能代表 apo 形式的结构。ABCB10-BV 形成封闭构象，胆绿素位于一个单体的疏水口袋中，并通过氢键与对面单体相互作用。我们还鉴定了夹在 BVs 之间的胆固醇，并基于这些结构和生化观察讨论了外排动力学。
