Chemical and Biomolecular Engineering, Department of

 

ORCID IDs

http://orcid.org/0000-0002-9383-1107

http://orcid.org/0000-0003-2980-4646

http://orcid.org/0000-0001-6807-5103

http://orcid.org/0000-0001-6983-9953

http://orcid.org/0000-0003-3826-1276

Date of this Version

2020

Document Type

Article

Citation

ATURE COMMUNICATIONS | (2020)11:4820 | https://doi.org/10.1038/s41467-020-18629-9 | www.nature.com/naturecommunications

Comments

The Author(s) 2020

Abstract

Protein tyrosine O-sulfation (PTS) plays a crucial role in extracellular biomolecular interac- tions 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.

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