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Analysis of residue–residue interactions in the structures of ASIC1a suggests possible gating mechanisms

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Abstract

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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Fig. 1
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Data availability

The data that support the findings of this study are available from the corresponding author, [DBT] upon request.

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Funding

This work is supported by RSF grant 21-14-00280 to DBT.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia

    Vyacheslav S. Korkosh & Denis B. Tikhonov

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  1. Vyacheslav S. Korkosh
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  2. Denis B. Tikhonov
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Contributions

VSK: calculations, data analysis, manuscript preparation. DBT: project design, data analysis, manuscript preparation.

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Correspondence to Denis B. Tikhonov.

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Korkosh, V.S., Tikhonov, D.B. Analysis of residue–residue interactions in the structures of ASIC1a suggests possible gating mechanisms. Eur Biophys J 52, 111–119 (2023). https://doi.org/10.1007/s00249-023-01628-1

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  • DOI: https://doi.org/10.1007/s00249-023-01628-1

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