Engineering of a Small Protein Scaffold to Recognize Sulfotyrosine with High Specificity

Justin Lawrie, Sean Waldrop, Anya Morozov, Wei Niu, Jiantao Guo

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Protein tyrosine O-sulfation is an essential post-translational modification required for effective biological processes such as hemostasis, inflammatory response, and visual phototransduction. Because of its unstable nature under mass spectrometry conditions and residing on low-abundance cell surface proteins, sulfated tyrosine (sulfotyrosine) residues are difficult to detect or analyze. Enrichment of sulfotyrosine-containing proteins (sulfoproteins) from complex biological samples are typically required before analysis. In this work, we seek to engineer the phosphotyrosine binding pocket of a Src Homology 2 (SH2) domain to act as an antisulfotyrosine antibody mimic. Using tailored selection schemes, several SH2 mutants are identified with high affinity and specificity to sulfotyrosine. Further molecular docking simulations highlight potential mechanisms supporting observed characteristics of these SH2 mutants. Utilities of the evolved SH2 mutants were demonstrated by the detection and enrichment of sulfoproteins.

Original languageEnglish (US)
Pages (from-to)1508-1517
Number of pages10
JournalACS chemical biology
Issue number8
StatePublished - Aug 20 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


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