How ATP binding and hydrolysis directionally reshape the conformational landscape remains unknown for ATP-binding cassette (ABC) transporters. Here, we identify two conserved ionic locks within the nucleotide-binding domains that govern transition barriers and energy transduction: an intra-subunit inward-facing (IF)-lock and an inter-subunit outward-facing (OF)-lock. Mg2+-ATP acts as a molecular key that disrupts the IF-lock, driving the forward transition. Following ATP hydrolysis, release of the {gamma}-phosphate, which, together with Mg2+, forms the pivot of the OF-lock, initiates the reverse transition. Directionality arises from kinetic asymmetry, driven by an anticorrelated exchange of the rate-limiting step between the consensus nucleotide-binding site and the transmembrane domains during forward and reverse transitions, respectively. Conservation of these molecular locks reveals a universal blueprint for ATP-driven mechanical transduction across the ABC superfamily.
Rudolph, M., Batebi, H., Pramod, M., Barth, K., Hirschberg, C., Tampe, R., Netz, R. R., Joseph, B.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 12
- Comments 0