Versatile and Efficient Site-Specific Protein Functionalization by Tubulin Tyrosine Ligase
Dominik Schumacher1,2, Jonas Helma3, Florian A Mann1,2
1Chemical Biology, Leibniz-Institut für Molekulare Pharmakologie, Berlin (Germany).
Abstract:
A novel chemoenzymatic approach for simple and fast site-specific protein labeling is reported. Recombinant tubulin tyrosine ligase (TTL) was repurposed to attach various unnatural tyrosine derivatives as small bioorthogonal handles to proteins containing a short tubulin-derived recognition sequence (Tub-tag). This novel strategy enables a broad range of high-yielding and fast chemoselective C-terminal protein modifications on isolated proteins or in cell lysates for applications in biochemistry, cell biology, and beyond, as demonstrated by the site-specific labeling of nanobodies, GFP, and ubiquitin.
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