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Molecular Spatiomics by Proximity Labeling

[Image: see text] Proximity labeling can be defined as an enzymatic “in-cell” chemical reaction that catalyzes the proximity-dependent modification of biomolecules in live cells. Since the modified proteins can be isolated and identified via mass spectrometry, this method has been successfully utili...

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Autores principales: Kang, Myeong-Gyun, Rhee, Hyun-Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118551/
https://www.ncbi.nlm.nih.gov/pubmed/35512328
http://dx.doi.org/10.1021/acs.accounts.2c00061
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author Kang, Myeong-Gyun
Rhee, Hyun-Woo
author_facet Kang, Myeong-Gyun
Rhee, Hyun-Woo
author_sort Kang, Myeong-Gyun
collection PubMed
description [Image: see text] Proximity labeling can be defined as an enzymatic “in-cell” chemical reaction that catalyzes the proximity-dependent modification of biomolecules in live cells. Since the modified proteins can be isolated and identified via mass spectrometry, this method has been successfully utilized for the characterization of local proteomes such as the sub-mitochondrial proteome and the proteome at membrane contact sites, or spatiotemporal interactome information in live cells, which are not “accessible” via conventional methods. Currently, proximity labeling techniques can be applied not only for local proteome mapping but also for profiling local RNA and DNA, in addition to showing great potential for elucidating spatial cell–cell interaction networks in live animal models. We believe that proximity labeling has emerged as an essential tool in “spatiomics,” that is, for the extraction of spatially distributed biological information in a cell or organism. Proximity labeling is a multidisciplinary chemical technique. For a decade, we and other groups have engineered it for multiple applications based on the modulation of enzyme chemistry, chemical probe design, and mass analysis techniques that enable superior mapping results. The technique has been adopted in biology and chemistry. This “in-cell” reaction has been widely adopted by biologists who modified it into an in vivo reaction in animal models. In our laboratory, we conducted in vivo proximity labeling reactions in mouse models and could successfully obtain the liver-specific secretome and muscle-specific mitochondrial matrix proteome. We expect that proximity reaction can further contribute to revealing tissue-specific localized molecular information in live animal models. Simultaneously, chemists have also adopted the concept and employed chemical “photocatalysts” as artificial enzymes to develop new proximity labeling reactions. Under light activation, photocatalysts can convert the precursor molecules to the reactive species via electron transfer or energy transfer and the reactive molecules can react with proximal biomolecules within a definite lifetime in an aqueous solution. To identify the modified biomolecules by proximity labeling, the modified biomolecules should be enriched after lysis and sequenced using sequencing tools. In this analysis step, the direct detection of modified residue(s) on the modified proteins or nucleic acids can be the proof of their labeling event by proximal enzymes or catalysts in the cell. In this Account, we introduce the basic concept of proximity labeling and the multidirectional advances in the development of this method. We believe that this Account may facilitate further utilization and modification of the method in both biological and chemical research communities, thereby revealing unknown spatially distributed molecular or cellular information or spatiome.
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spelling pubmed-91185512022-05-20 Molecular Spatiomics by Proximity Labeling Kang, Myeong-Gyun Rhee, Hyun-Woo Acc Chem Res [Image: see text] Proximity labeling can be defined as an enzymatic “in-cell” chemical reaction that catalyzes the proximity-dependent modification of biomolecules in live cells. Since the modified proteins can be isolated and identified via mass spectrometry, this method has been successfully utilized for the characterization of local proteomes such as the sub-mitochondrial proteome and the proteome at membrane contact sites, or spatiotemporal interactome information in live cells, which are not “accessible” via conventional methods. Currently, proximity labeling techniques can be applied not only for local proteome mapping but also for profiling local RNA and DNA, in addition to showing great potential for elucidating spatial cell–cell interaction networks in live animal models. We believe that proximity labeling has emerged as an essential tool in “spatiomics,” that is, for the extraction of spatially distributed biological information in a cell or organism. Proximity labeling is a multidisciplinary chemical technique. For a decade, we and other groups have engineered it for multiple applications based on the modulation of enzyme chemistry, chemical probe design, and mass analysis techniques that enable superior mapping results. The technique has been adopted in biology and chemistry. This “in-cell” reaction has been widely adopted by biologists who modified it into an in vivo reaction in animal models. In our laboratory, we conducted in vivo proximity labeling reactions in mouse models and could successfully obtain the liver-specific secretome and muscle-specific mitochondrial matrix proteome. We expect that proximity reaction can further contribute to revealing tissue-specific localized molecular information in live animal models. Simultaneously, chemists have also adopted the concept and employed chemical “photocatalysts” as artificial enzymes to develop new proximity labeling reactions. Under light activation, photocatalysts can convert the precursor molecules to the reactive species via electron transfer or energy transfer and the reactive molecules can react with proximal biomolecules within a definite lifetime in an aqueous solution. To identify the modified biomolecules by proximity labeling, the modified biomolecules should be enriched after lysis and sequenced using sequencing tools. In this analysis step, the direct detection of modified residue(s) on the modified proteins or nucleic acids can be the proof of their labeling event by proximal enzymes or catalysts in the cell. In this Account, we introduce the basic concept of proximity labeling and the multidirectional advances in the development of this method. We believe that this Account may facilitate further utilization and modification of the method in both biological and chemical research communities, thereby revealing unknown spatially distributed molecular or cellular information or spatiome. American Chemical Society 2022-05-05 2022-05-17 /pmc/articles/PMC9118551/ /pubmed/35512328 http://dx.doi.org/10.1021/acs.accounts.2c00061 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Kang, Myeong-Gyun
Rhee, Hyun-Woo
Molecular Spatiomics by Proximity Labeling
title Molecular Spatiomics by Proximity Labeling
title_full Molecular Spatiomics by Proximity Labeling
title_fullStr Molecular Spatiomics by Proximity Labeling
title_full_unstemmed Molecular Spatiomics by Proximity Labeling
title_short Molecular Spatiomics by Proximity Labeling
title_sort molecular spatiomics by proximity labeling
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118551/
https://www.ncbi.nlm.nih.gov/pubmed/35512328
http://dx.doi.org/10.1021/acs.accounts.2c00061
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