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Mapping the conformational wave of acetylcholine receptor channel gating

Author

Listed:
  • Claudio Grosman

    (State University of New York at Buffalo, 124 Sherman Hall)

  • Ming Zhou

    (State University of New York at Buffalo, 124 Sherman Hall)

  • Anthony Auerbach

    (State University of New York at Buffalo, 124 Sherman Hall)

Abstract

Allosteric transitions allow fast regulation of protein function in living systems. Even though the end points of such conformational changes are known for many proteins, the characteristics of the paths connecting these states remain largely unexplored. Rate-equilibrium linear free-energy relationships (LFERs) provide information about such pathways by relating changes in the free energy of the transition state to those of the ground states upon systematic perturbation of the system1. Here we present an LFER analysis of the gating reaction pathway of the muscle acetylcholine receptor. We studied the closed ⇌ open conformational change at the single-molecule level following perturbation by series of single-site mutations, agonists and membrane voltages. This method provided a snapshot of several regions of the receptor at the transition state in terms of their approximate positions along the reaction coordinate, on a scale from 0 (closed-like) to 1 (open-like). The resulting map reveals a spatial gradient of positional values, which suggests that the conformational change proceeds in a wave-like manner, with the low-to-high affinity change at the transmitter-binding sites preceding the complete opening of the pore.

Suggested Citation

  • Claudio Grosman & Ming Zhou & Anthony Auerbach, 2000. "Mapping the conformational wave of acetylcholine receptor channel gating," Nature, Nature, vol. 403(6771), pages 773-776, February.
    • Handle: RePEc:nat:nature:v:403:y:2000:i:6771:d:10.1038_35001586
    DOI: 10.1038/35001586
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    Cited by:

    1. Do Hoon Kwon & Feng Zhang & Justin G. Fedor & Yang Suo & Seok-Yong Lee, 2022. "Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Mohammed Atif & Argel Estrada-Mondragon & Bindi Nguyen & Joseph W Lynch & Angelo Keramidas, 2017. "Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus," PLOS Pathogens, Public Library of Science, vol. 13(10), pages 1-30, October.
    3. David Mowrey & Qiang Chen & Yuhe Liang & Jie Liang & Yan Xu & Pei Tang, 2013. "Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-8, May.
    4. Dinesh C Indurthi & Trevor M Lewis & Philip K Ahring & Thomas Balle & Mary Chebib & Nathan L Absalom, 2016. "Ligand Binding at the α4-α4 Agonist-Binding Site of the α4β2 nAChR Triggers Receptor Activation through a Pre-Activated Conformational State," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-20, August.

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