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Morozov, A. 2021. Engineering Src Homology 2 Domains with Improved Specificity for Sulfotyrosine. Honors Undergraduate Thesis. University of Nebraska-Lincoln.


Copyright Anya Morozov 2021.


Protein tyrosine O-sulfation (PTS) is a common post-translational modification that has been implicated in a variety of biological processes and human illnesses. Despite continued progress in the field of sulfoproteomics, the extent and function of sulfated tyrosine (sulfotyrosine) residues is a topic of ongoing research. Previous work in the Guo Lab has identified Src Homology-2 (SH2) mutants that have a high affinity for sulfotyrosine along with retained high affinity for their natural ligand, phosphorylated tyrosine (phosphotyrosine). In this thesis, I attempted to generate SH2 mutants that have high affinity and specificity for sulfotyrosine over phosphotyrosine. While I successfully generated SH2 libraries and conducted a series of selections, I was not able to identify any SH2 mutants with desirable properties. Although the challenging research was not achieved in this thesis, there is still much to be learned from a careful examination of the methods employed here and of the literature surrounding the creation of small molecule binders through library design and phage display technology.

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