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Functional genetic encoding of sulfotyrosine in mammalian cells

Author

Listed:
  • Xinyuan He

    (University of Nebraska-Lincoln)

  • Yan Chen

    (University of Nebraska-Lincoln)

  • Daisy Guiza Beltran

    (University of Nebraska-Lincoln)

  • Maia Kelly

    (University of Nebraska-Lincoln)

  • Bin Ma

    (University of Nebraska-Lincoln)

  • Justin Lawrie

    (University of Nebraska-Lincoln)

  • Feng Wang

    (Chinese Academy of Sciences)

  • Eric Dodds

    (University of Nebraska-Lincoln)

  • Limei Zhang

    (University of Nebraska-Lincoln)

  • Jiantao Guo

    (University of Nebraska-Lincoln)

  • Wei Niu

    (University of Nebraska-Lincoln)

Abstract

Protein tyrosine O-sulfation (PTS) plays a crucial role in extracellular biomolecular interactions that dictate various cellular processes. It also involves in the development of many human diseases. Regardless of recent progress, our current understanding of PTS is still in its infancy. To promote and facilitate relevant studies, a generally applicable method is needed to enable efficient expression of sulfoproteins with defined sulfation sites in live mammalian cells. Here we report the engineering, in vitro biochemical characterization, structural study, and in vivo functional verification of a tyrosyl-tRNA synthetase mutant for the genetic encoding of sulfotyrosine in mammalian cells. We further apply this chemical biology tool to cell-based studies on the role of a sulfation site in the activation of chemokine receptor CXCR4 by its ligand. Our work will not only facilitate cellular studies of PTS, but also paves the way for economical production of sulfated proteins as therapeutic agents in mammalian systems.

Suggested Citation

  • Xinyuan He & Yan Chen & Daisy Guiza Beltran & Maia Kelly & Bin Ma & Justin Lawrie & Feng Wang & Eric Dodds & Limei Zhang & Jiantao Guo & Wei Niu, 2020. "Functional genetic encoding of sulfotyrosine in mammalian cells," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18629-9
    DOI: 10.1038/s41467-020-18629-9
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    Cited by:

    1. Yuda Chen & Shikai Jin & Mengxi Zhang & Yu Hu & Kuan-Lin Wu & Anna Chung & Shichao Wang & Zeru Tian & Yixian Wang & Peter G. Wolynes & Han Xiao, 2022. "Unleashing the potential of noncanonical amino acid biosynthesis to create cells with precision tyrosine sulfation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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