Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

Original languageEnglish (US)
Pages (from-to)2551-2557
Number of pages7
JournalACS Chemical Biology
Volume11
Issue number9
DOIs
StatePublished - Sep 16 2016

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src Homology Domains
Tyrosine
Post Translational Protein Processing
Phosphotyrosine
Proteins
Bacteriophages
Scaffolds
Design of experiments
Display devices
Research Design
tyrosine O-sulfate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine. / Ju, Tong; Niu, Wei; Guo, Jiantao.

In: ACS Chemical Biology, Vol. 11, No. 9, 16.09.2016, p. 2551-2557.

Research output: Contribution to journalArticle

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