Journal
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
Volume 52, Issue 1-2, Pages 111-119Publisher
SPRINGER
DOI: 10.1007/s00249-023-01628-1
Keywords
Ion channels; Molecular modeling; Gaiting mechanism; Residue-residue interactions; Proton recognition
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The gating mechanism of ASICs is still not clear despite atomic-scale structures being available. Activation is assumed to be triggered by the collapse of the acidic pocket and structural changes in the low-palm region. Protonation of certain residues in the acidic pocket can minimize repulsion in the collapsed conformation. Our study supports a proposal of a gating mechanism in the low-palm region involving residues E80 and E417 sharing a proton.
The gating mechanism of acid-sensitive ion channels (ASICs) remains unclear, despite the availability of atomic-scale structures in various functional states. The collapse of the acidic pocket and structural changes in the low-palm region are assumed to trigger activation. For the acidic pocket, protonation of some residues can minimize repulsion in the collapsed conformation. The relationship between low-palm rearrangements and gating is unknown. In this work, we performed a Monte Carlo energy optimization of known ASIC1a structures and determined the residue-residue interactions in different functional states. For rearrangements in the acidic pocket, our results are consistent with previously proposed mechanisms, although significant complexity was revealed for the residue-residue interactions. The data support the proposal of a gating mechanism in the low-palm region, in which residues E80 and E417 share a proton to activate the channel.
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