Journal article
Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology
Chemical reviews, Vol.124(20), pp.11523-11543
08/29/2024
DOI: 10.1021/acs.chemrev.4c00306
PMCID: PMC11503617
PMID: 39207057
Appears in UI Libraries Support Open Access
Abstract
Ion channels play central roles in biology and human health by catalyzing the transmembrane flow of electrical charge. These proteins are ideal targets for genetic code expansion (GCE) methods because it is feasible to measure ion channel activity from miniscule amounts of protein and to analyze the resulting data via rigorous, established biophysical methods. In an ideal scenario, the encoding of synthetic, noncanonical amino acids via GCE allows the experimenter to ask questions inaccessible to traditional methods. For this reason, GCE has been successfully applied to a variety of ligand- and voltage-gated channels wherein extensive structural, functional, and pharmacological data exist. Here, we provide a comprehensive summary of GCE as applied to ion channels. We begin with an overview of the methods used to encode noncanonical amino acids in channels and then describe mechanistic studies wherein GCE was used for photochemistry (cross-linking; caged amino acids) and atomic mutagenesis (isosteric manipulation of charge and aromaticity; backbone mutation). Lastly, we cover recent advances in the encoding of fluorescent amino acids for the real-time study of protein conformational dynamics.
Details
- Title: Subtitle
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology
- Creators
- Daniel T. Infield - University of IowaMiranda E. Schene - University of IowaJason D. Galpin - University of IowaChristopher A. Ahern - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical reviews, Vol.124(20), pp.11523-11543
- DOI
- 10.1021/acs.chemrev.4c00306
- PMID
- 39207057
- PMCID
- PMC11503617
- NLM abbreviation
- Chem Rev
- ISSN
- 0009-2665
- eISSN
- 1520-6890
- Publisher
- American Chemical Society
- Grant note
- NIH/NIGMS: R35GM148239 NIH/NIDS: R24NS104617
C.A.A. and J.D.G. are supported by NIH/NIGMS R35GM148239 "Chemical biology of voltage-gated cation channels", 2/2023-01/2028, and NIH/NIDS R24NS104617 "The Facility for Atomic Mutagenesis", 12/2017-11/2022.D.T.I. was supported by F32HL149184 "Chemical Biology of CFTR Regulation", 7/2019-6/2022. M.E.S. is supported by F30HL165692"Using a Molecular Toolkit to Examine Potassium Channel Gating and Regulation", 9/2022-8/2026.
- Language
- English
- Date published
- 08/29/2024
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984701408102771
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