The abstract is read at the publisher; the summary is JClub's.
All-atom simulations and biochemical assays of AAA+ unfoldases Yme1 and Vps4 identify two allosteric networks that couple hydrolysis and pore-loop dynamics to position-dependent substrate release.
- Why it matters: Directional peptide translocation in AAA+ motors must reconcile cryo-EM–inspired hand-over-hand asymmetry with variable, stochastic step sizes, but the structural basis for kinetic bias is unclear.
- What they did: The study combines all-atom simulations with biochemical assays to map conformational changes after hydrolysis, ADP release, and ATP association, then tests network function using mutational disruption and nucleotide-exchange intermediates.
- The result: One network links Walker B glutamate to the proximal subunit nucleotide binding pocket to propagate hydrolysis competence backward, while the second couples nucleotide binding and salt-bridge rearrangements to pore-loop dynamics; disrupting the second network inhibits substrate degradation more than ATP hydrolysis.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.