BPS2026 – Molecular turnstiles: Following ABC transporters in motion

Proteins embedded in the cell membrane act as gatekeepers that regulate the selective movement of compounds into and out of the cell. Among the most widespread and functionally important of these are ATP-binding cassette (ABC) transporters, which harness the energy of ATP hydrolysis to drive substrate translocation. In bacteria, ABC importers are indispensable for survival, as they control the uptake of nutrients and metals scavenged from the environment. Defects in these systems often result in reduced bacterial fitness, impaired growth, and diminished biofilm formation. Importantly, the tight regulation of transport ensures that essential nutrients do not accumulate to toxic levels, striking a balance between sufficiency and toxicity. Using a combination of cryo-electron microscopy (cryo-EM) and electron paramagnetic resonance spectroscopy (EPR), we provide new insights into how organisms employ transport systems to achieve precise control over nutrient influx with remarkable substrate specificity. Structural studies revealed previously uncharacterized confirmations in the transport cycle that were not detected earlier in structural studies. These findings expand the current understanding of the mechanistic and structural diversity of bacterial ABC importers, suggesting that their repertoire of conformational states in substrate recognition strategies is broader than previously appreciated.