Squeeze pumping of lipids and insecticides by ABCH transporter

Jinli Chen; Yanwei Duan; Yuanyuan Zhou; Qing Yang

doi:10.1016/j.cell.2024.11.033

Squeeze pumping of lipids and insecticides by ABCH transporter

Cell. 2024 Dec 18:S0092-8674(24)01375-8. doi: 10.1016/j.cell.2024.11.033. Online ahead of print.

Authors

Jinli Chen¹, Yanwei Duan², Yuanyuan Zhou³, Qing Yang⁴

Affiliations

¹ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China; Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
² Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
³ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China; School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
⁴ State Key Laboratory for Biology of Plant Diseases and Insect Pests, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China; Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: qingyang@caas.cn.

PMID: 39721587
DOI: 10.1016/j.cell.2024.11.033

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.

Keywords: ABC transporter; ABCH; insecticide resistance; lipid transport.