Protein engineering and design in ion channels and receptors.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0373334 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 0091-679X (Print) Linking ISSN: 0091679X NLM ISO Abbreviation: Methods Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Academic Press
    • Subject Terms:
      Ion Channels*/genetics ; Ion Channels*/metabolism ; Protein Engineering*; Molecular Conformation ; Thermodynamics
    • Abstract:
      Acetylcholine receptors (AChRs) expressed at the neuromuscular junction synapses are typical allosteric proteins that shuttle between at least two stable conformational states: Closed (C) and Open (O). Agonist binding to their target sites on the receptor in the extracellular domain triggers a global C→O conformational change that results in an open channel pore that allows ion conduction. How the receptor senses the chemical signal of an agonist and communicates it to the channel pore, located ~50Å away, are key to understanding the receptor function. AChRs are indispensable for muscle contraction and their neuronal homologues play critical roles in the nervous system function. In this chapter, using a combination of single channel patch-clamp, computational approaches, and genetic engineering, we elucidate the principles of design and engineering to quantify the fundamental thermodynamic parameters of AChRs that regulate ligand binding and channel opening. The receptor engineering principles outlined here for the neuromuscular AChRs are applicable to the broader class of ligand-gated ion channel proteins.
      (Copyright © 2022 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Affinity; Allostery; Efficacy; Molecular dynamics; Patch-clamp; Thermodynamics
    • Accession Number:
      0 (Ion Channels)
    • Publication Date:
      Date Created: 20220527 Date Completed: 20220531 Latest Revision: 20220601
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/bs.mcb.2021.12.031
    • Accession Number:
      35623700