Mechanistic basis of plant hormone transport by ABC transporters: Insights from cryo-EM structures

The ATP-binding cassette (ABC) transporters constitute a large superfamily of proteins that utilize the energy from ATP hydrolysis to transport diverse substrates across biological membranes. In plants, ABC transporters play significant roles in the translocation of phytohormones, essential for growth, development, and stress responses. For decades, the mechanistic understanding of how these transporters recognize and transport hormones remained speculative, relying on primarily genetic and biochemical studies. Recent advances in cryo-EM have overcome these limitations, enabling the structure determination of plant hormone ABC transporters in different states at 2-4 Å resolution. This review summarizes the latest structural breakthroughs on four plant ABC transporters: the abscisic acid exporter ABCG25, the jasmonic acid exporter ABCG16 and the brassinosteroid exporters ABCB19 and ABCB1. By comparing the structures, the structural determinants underlying the functional divergence of these transporter families are uncovered. Specific substrate-binding pockets that define selectivity are identified, offering predictive power for locating functional homologs across the plant kingdom. The mechanistic variations in their ATPase activities are further delineated, detailing the unique enzymatic mechanisms by which energy coupling is governed. These revelations about alternative-access transport mechanisms offer a new framework for understanding protein evolution. Ultimately, the gap between hormone signaling and transporter function is bridged by these structural knowledges, opening novel avenues for engineering crops with optimized hormonal responses.