Structural Superimposition

Abstact

Plants are highly vulnerable to damage from environmental pollutants, making detoxification mechanisms essential for sustaining growth and development. ABCC2 in Arabidopsis thaliana (AtABCC2) plays a critical role in detoxification by exporting diverse toxic compounds. Here, we report the structures of AtABCC2 in three distinct states: substrate-free, bound to the substrate S-(2,4-dinitrophenyl)glutathione (DNP-GS), and bound to ATP. Both monomeric and dimeric forms of AtABCC2 are observed. Unlike other dimeric ABCC homologs, AtABCC2 features a dimer interface mediated by its transmembrane domains. DNP-GS occupies an amphipathic cavity formed by the transmembrane domains. ATP binding drives the conformational changes in each protomer which bring the transmembrane and nucleotide-binding domains closer together, transitioning the transporter from a cytosolic-facing to an occluded state. Together, these findings advance our understanding of the molecular basis of substrate binding and transport by AtABCC2, and shed light on plant detoxification mechanisms.