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A stepwise mechanism for acetylcholine receptor channel gating

Author

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  • Prasad Purohit

    (State University of New York at Buffalo, Buffalo, New York 14214, USA)

  • Ananya Mitra

    (State University of New York at Buffalo, Buffalo, New York 14214, USA)

  • Anthony Auerbach

    (State University of New York at Buffalo, Buffalo, New York 14214, USA)

Abstract

Muscle contraction is triggered by the opening of acetylcholine receptors at the vertebrate nerve–muscle synapse1,2,3,4. The M2 helix of this allosteric membrane protein lines the channel, and contains a ‘gate’ that regulates the flow of ions through the pore. We used single-molecule kinetic analysis to probe the transition state of the gating conformational change and estimate the relative timing of M2 motions in the α-subunit of the murine acetylcholine receptor5. This analysis produces a ‘Φ-value’ for a given residue that reflects its open-like versus closed-like character at the transition state. Here we show that most of the residues throughout the length of M2 have a Φ-value of ∼0.64 but that some near the middle have lower Φ-values of 0.52 or 0.31, suggesting that αM2 moves in three discrete steps. The core of the channel serves both as a gate that regulates ion flow and as a hub that directs the propagation of the gating isomerization through the membrane domain of the acetylcholine receptor.

Suggested Citation

  • Prasad Purohit & Ananya Mitra & Anthony Auerbach, 2007. "A stepwise mechanism for acetylcholine receptor channel gating," Nature, Nature, vol. 446(7138), pages 930-933, April.
    • Handle: RePEc:nat:nature:v:446:y:2007:i:7138:d:10.1038_nature05721
    DOI: 10.1038/nature05721
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    Cited by:

    1. Pallavi A Bafna & Prasad G Purohit & Anthony Auerbach, 2008. "Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap," PLOS ONE, Public Library of Science, vol. 3(6), pages 1-10, June.

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