中国农业科学院深圳农业基因组研究所杨青团队发现，ABCH转运蛋白通过挤压泵出脂质和杀虫剂。2024年12月24日，《细胞》杂志在线发表了这项成果。

研究人员报告了来自储粮害虫赤拟谷盗（Tribolium castaneum）的ABCH转运蛋白的冷冻电镜（cryo-EM）结构，该转运蛋白与HEK293细胞-神经酰胺脂质、荧光标记神经酰胺、氨基甲酸酯类杀虫剂和麦芽糖去垢剂抑制剂形成复合物。

研究人员揭示了转运蛋白二聚体的跨膜域中一个狭窄、长且弯曲的底物结合通道，并发现有两个由精氨酸门控的胞内入口用于脂质或杀虫剂的结合和运输。一对谷氨酰胺位于通道上方，作为门控指引底物在ATP结合后，通过类似通风口的亲水性出口被挤出到膜的细胞外侧。

这些结构和生化数据为脂质运输、杀虫剂解毒，以及支链麦芽糖去垢剂抑制转运蛋白活性，提供了机制性理解。

据悉，ATP结合盒（ABC）转运蛋白H亚家族仅在节肢动物和斑马鱼中被发现。它运输脂质，并与杀虫剂抗性相关。然而，其功能的精确机制仍不明确。

附：英文原文

Title: Squeeze pumping of lipids and insecticides by ABCH transporter

Author: Jinli Chen, Yanwei Duan, Yuanyuan Zhou, Qing Yang

Issue&Volume: 2024-12-24

Abstract: 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.

DOI: 10.1016/j.cell.2024.11.033

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01375-8