Squeeze pumping of lipids and insecticides by ABCH transporter

文献类型： 外文期刊

第一作者： Chen, Jinli

作者： Chen, Jinli;Zhou, Yuanyuan;Yang, Qing;Chen, Jinli;Duan, Yanwei;Yang, Qing;Chen, Jinli;Zhou, Yuanyuan

作者机构：

期刊名称：CELL （ 影响因子：42.5； 五年影响因子：48.9 ）

ISSN： 0092-8674

年卷期： 2025 年 188 卷 4 期

页码：

收录情况： SCI

摘要： ATP-binding cassette (ABC) transporter subfamily H is only identified in arthropods and zebrafish. It transports lipids and is related to insecticide resistance. However, the precise mechanisms of its functions remain elusive. Here, we report cryoelectron microscopy (cryo-EM) structures of an ABCH from Tribolium castaneum, a worldwide pest of stored grains, in complex with an HEK293 cell-ceramide lipid, a fluorescent- labeled ceramide, a carbamate insecticide, and a maltose detergent inhibitor. We revealed a narrow, long, and arched substrate-binding tunnel in the transmembrane domains of the transporter dimer with two arginine-gated cytoplasmic entries for the binding and transport of lipids or insecticides. A pair of glutamines above the tunnel acts as a gate for directing substrate to be extruded via a vent-like hydrophilic exit to the extracellular side of the membrane upon ATP binding. Our structures and biochemical data provide mechanistic understanding of lipid transport, insecticide detoxification, and the inhibition of transporter activity by branched maltose detergents.

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