PIN auxin transporters facilitate polar transport of synthetic phenoxyacetic acid herbicides

Synthetic herbicides are widely used in agriculture to control weeds, often by targeting the physiological pathways regulated by auxins, plant hormones that induce root growth and development. PIN-FORMED (PIN) auxin transporters facilitate the polar transport of natural auxins such as indole-3-acetic acid (IAA) out of the cell. To determine whether phenoxyacetic acid herbicides (synthetic auxins) are similarly transported by PIN transporters, Schulz and coworkers evaluated the transport kinetics of synthetic auxins via PIN8. The authors found that 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chlorophenoxyacetic acid (4-CPA) were transported in the presence of PIN8, with transport kinetics resembling IAA. Notably, the binding affinity varied depending on the chemical structure of the substrates. Using Cryo-EM, the authors resolved the structure of PIN8 and explored the molecular interactions that direct the transport dynamics. Five conformations occur during the transport event, which reflect a multistep process that involves substrate recognition, binding, and release. Structure-guided mutagenesis further identified key residues determining substrate specificity. The configuration of the binding site directs the substrate movement to the vestibule of the transporter and out of the cell. This study lays the groundwork for the identification and design of novel herbicides, as well as for the manipulation of plant physiology to confer herbicide resistance through synthetic biochemistry and protein engineering. (Summary by Jerry González Cantoral @phytojerry.bsky.social) Nature Plants. 10.1038/s41477-025-01984-0