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Functional genetic encoding of sulfotyrosine in mammalian cells.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

He X,Chen Y,Beltran DG,Kelly M,Ma B,Lawrie J,Wang F,Dodds E,Zhang L,Guo J,Niu W

doi

10.1038/s41467-020-18629-9

subject

Has Abstract

pub_date

2020-09-24 00:00:00

pages

4820

issue

1

issn

2041-1723

pii

10.1038/s41467-020-18629-9

journal_volume

11

pub_type

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