Kinetic asymmetry drives directionality in an ATP-binding cassette transporter
- 1Freie Universitaet Berlin
Abstract
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.
Related
- Substrate binding reorganizes the energetic landscape of Plasmodium falciparum hexose transporter PfHT1
- A rapid, automation-friendly, cell-free and purification-free pipeline for binding and kinetic characterisation of de novo designed binders with high quality standardised per-design data
- Network-based integration of cross-dataset proteomic profiles using fold-change directionality.
- Streamlining recombinant peptide and protein production using a pre-configured elastin-like polypeptide expression cassette
- Reference-signature projection framework for exercise transcriptomic directionality based on the IAV-DI reference axis.
BibTeX
@misc{rudolph2026kinetic,
title = {{Kinetic asymmetry drives directionality in an ATP-binding cassette transporter}},
author = {M. Rudolph and H. Batebi and M. Pramod and K. Barth and C. Hirschberg and R. Tampe and R. R. Netz and B. Joseph},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.751009},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.751009v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Kinetic asymmetry drives directionality in an ATP-binding cassette transporter
AU - M. Rudolph
AU - H. Batebi
AU - M. Pramod
AU - K. Barth
AU - C. Hirschberg
AU - R. Tampe
AU - R. R. Netz
AU - B. Joseph
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.751009
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.751009v1
AB - 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.
ER -