Chimeras of KcsA and Kv1 as a bioengineering tool to study voltage-gated potassium channels and their ligands
- PMID: 34090876
- DOI: 10.1016/j.bcp.2021.114646
Chimeras of KcsA and Kv1 as a bioengineering tool to study voltage-gated potassium channels and their ligands
Abstract
Chimeric potassium channels KcsA-Kv1, which are among the most intensively studied hybrid membrane proteins to date, were constructed by replacing a part of the pore domain of bacterial potassium channel KcsA (K channel of streptomyces A) with corresponding regions of the mammalian voltage-gated potassium channels belonging to the Kv1 subfamily. In this way, the pore blocker binding site of Kv1 channels was transferred to KcsA, opening up possibility to use the obtained hybrids as receptors of Kv1-channel pore blockers of different origin. In this review the recent progress in KcsA-Kv1 channel design and applications is discussed with a focus on the development of new assays for studying interactions of pore blockers with the channels. A summary of experimental data is presented demonstrating that hybrid channels reproduce the blocker-binding profiles of parental Kv1 channels. It is overviewed how the KcsA-Kv1 chimeras are used to get new insight into the structure of potassium channels, to determine molecular basis for high affinity and selectivity of binding of peptide blockers to Kv1 channels, as well as to identify new peptide ligands.
Keywords: Chimeric channels; Kv1, KcsA; Ligands; Voltage-gated potassium channels.
Copyright © 2021 Elsevier Inc. All rights reserved.
Similar articles
-
Complexes of Peptide Blockers with Kv1.6 Pore Domain: Molecular Modeling and Studies with KcsA-Kv1.6 Channel.J Neuroimmune Pharmacol. 2017 Jun;12(2):260-276. doi: 10.1007/s11481-016-9710-9. Epub 2016 Sep 17. J Neuroimmune Pharmacol. 2017. PMID: 27640211
-
Engineering-specific pharmacological binding sites for peptidyl inhibitors of potassium channels into KcsA.Biochemistry. 2002 Dec 24;41(51):15369-75. doi: 10.1021/bi026264a. Biochemistry. 2002. PMID: 12484776
-
KcsA-Kv1.x chimeras with complete ligand-binding sites provide improved predictivity for screening selective Kv1.x blockers.J Biol Chem. 2024 Apr;300(4):107155. doi: 10.1016/j.jbc.2024.107155. Epub 2024 Mar 11. J Biol Chem. 2024. PMID: 38479597 Free PMC article.
-
Potassium channels: structures, models, simulations.Biochim Biophys Acta. 2002 Oct 11;1565(2):294-307. doi: 10.1016/s0005-2736(02)00576-x. Biochim Biophys Acta. 2002. PMID: 12409202 Review.
-
Structure of the voltage-gated potassium channel KV1.3: Insights into the inactivated conformation and binding to therapeutic leads.Channels (Austin). 2023 Dec;17(1):2253104. doi: 10.1080/19336950.2023.2253104. Channels (Austin). 2023. PMID: 37695839 Free PMC article. Review.
Cited by
-
AgTx2-GFP, Fluorescent Blocker Targeting Pharmacologically Important Kv1.x (x = 1, 3, 6) Channels.Toxins (Basel). 2023 Mar 18;15(3):229. doi: 10.3390/toxins15030229. Toxins (Basel). 2023. PMID: 36977120 Free PMC article.
-
Atto488-Agitoxin 2-A Fluorescent Ligand with Increased Selectivity for Kv1.3 Channel Binding Site.Bioengineering (Basel). 2022 Jul 1;9(7):295. doi: 10.3390/bioengineering9070295. Bioengineering (Basel). 2022. PMID: 35877346 Free PMC article.
-
Neurotoxin-Derived Optical Probes for Biological and Medical Imaging.Mol Imaging Biol. 2023 Oct;25(5):799-814. doi: 10.1007/s11307-023-01838-1. Epub 2023 Jul 19. Mol Imaging Biol. 2023. PMID: 37468801 Free PMC article. Review.
-
Bioengineered System for High Throughput Screening of Kv1 Ion Channel Blockers.Bioengineering (Basel). 2021 Nov 16;8(11):187. doi: 10.3390/bioengineering8110187. Bioengineering (Basel). 2021. PMID: 34821753 Free PMC article.
-
GFP-Margatoxin, a Genetically Encoded Fluorescent Ligand to Probe Affinity of Kv1.3 Channel Blockers.Int J Mol Sci. 2022 Feb 2;23(3):1724. doi: 10.3390/ijms23031724. Int J Mol Sci. 2022. PMID: 35163644 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
