Engineered SH2 Domains for Targeted Phosphoproteomics.

ABSTRACT: A comprehensive analysis of the phosphoproteome is essential for understanding molecular mechanisms of human diseases. However, current tools used to enrich phosphotyrosine (pTyr) are limited in their applicability and scope. Here, we engineered new superbinder Src-Homology 2 (SH2) domains that enrich diverse sets of pTyr-peptides. We used phage display to select a Fes-SH2 domain variant (superFes; sFes¹) with high affinity for pTyr and solved its structure bound to a pTyr-peptide. We performed systematic structure-function analyses of the superbinding mechanisms of sFes¹ and superSrc-SH2 (sSrc¹), another SH2 superbinder. We grafted the superbinder motifs from sFes¹ and sSrc¹ into 17 additional SH2 domains and confirmed increased bindi

SUBMITTER: Martyn GD 

PROVIDER: S-EPMC9251651 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature