Genetic Code Expansion Enables Live-Cell and Super-Resolution Imaging of Site-Specifically Labeled Cellular Proteins.

Methods to site-specifically and densely label proteins in cellular ultrastructures with small, bright, and photostable fluorophores would substantially advance super-resolution imaging. Recent advances in genetic code expansion and bioorthogonal chemistry have enabled the site-specific labeling of...

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Publicado en:Journal of the American Chemical Society Vol. 137; no. 14; pp. 4602 - 4606
Autores principales: Uttamapinant, Chayasith, Howe, Jonathan D., Lang, Kathrin, Beránek, Václav, Davis, Lloyd, Mahesh, Mohan, Barry, Nicholas P., Chin, Jason W.
Formato: Artículo
Publicado: American Chemical Society 4/15/2015
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 4/15/2015
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        10.1021/ja512838z
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        atl: Genetic Code Expansion Enables Live-Cell and Super-Resolution Imaging of Site-Specifically Labeled Cellular Proteins.
      aug:
        au:
          Uttamapinant, Chayasith
          Howe, Jonathan D.
          Lang, Kathrin
          Beránek, Václav
          Davis, Lloyd
          Mahesh, Mohan
          Barry, Nicholas P.
          Chin, Jason W.
        affil:
          Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 OQH, United Kingdom
          Department of Chemistry, Technische Universitat Miinchen, Institute for Advanced Study, Lichtenbergstrasse 4, 85748 Garching, Germany
      su:
        Genetic code
        Proteins
        Fluorophores
        High resolution imaging
        Amino acids
      sug:
        subj:
          Genetic code
          Proteins
          Fluorophores
          High resolution imaging
          Amino acids
      ab: Methods to site-specifically and densely label proteins in cellular ultrastructures with small, bright, and photostable fluorophores would substantially advance super-resolution imaging. Recent advances in genetic code expansion and bioorthogonal chemistry have enabled the site-specific labeling of proteins. However, the efficient incorporation of unnatural amino acids into proteins and the specific, fluorescent labeling of the intracellular ultrastructures they form for subdiffraction imaging has not been accomplished. Two challenges have limited progress in this area: (i) the low efficiency of unnatural amino acid incorporation that limits labeling density and therefore spatial resolution and (ii) the uncharacterized specificity of intracellular labeling that will define signal-to-noise, and ultimately resolution, in imaging. Here we demonstrate the efficient production of cystoskeletal proteins (β-actin and vimentin) containing bicyclo [6.1.0]-nonyne-lysine at genetically defined sites. We demonstrate their selective fluorescent labeling with respect to the proteome of living cells using tetrazine-fluorophore conjugates, creating densely labeled cytoskeletal ultrastructures. STORM imaging of these densely labeled ultrastructures reveals subdiffraction features, including nuclear actin filaments. This work enables the site-specific, live-cell, fluorescent labeling of intracellular proteins at high density for super-resolution imaging of ultrastructural features within cells.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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          year: 2015
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