A chemical biology route to site-specific authentic protein modifications

Many essential biological processes are controlled by posttranslational protein modifications. The inability to synthetically attain the diversity enabled by these modifications limits functional studies of many proteins. We designed a three-step approach for installing authentic posttranslational modifications in recombinant proteins. We first use the established O-phosphoserine (Sep) orthogonal translation system to create a Sep-containing recombinant protein. The Sep residue is then dephosphorylated to dehydroalanine (Dha). Last, conjugate addition of alkyl iodides to Dha, promoted by zinc and copper, enables chemoselective carbon-carbon bond formation. To validate our approach, we produced histone H3, ubiquitin, and green fluorescent protein variants with site-specific modifications, including different methylations of H3K79. The methylated histones stimulate transcription through histone acetylation. This approach offers a powerful tool to engineer diverse designer proteins
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2016-11
Language
English
Keywords

POSTTRANSLATIONAL MODIFICATIONS; RECOMBINANT HISTONES; LYSINE ANALOGS; BOND FORMATION; METHYL-LYSINE; GENETIC-CODE; PHOSPHOSERINE; CHEMISTRY; CYSTEINE; PEPTIDE

Citation

SCIENCE, v.354, no.6312, pp.623 - 626

ISSN
0036-8075
DOI
10.1126/science.aah4428
URI
http://hdl.handle.net/10203/214602
Appears in Collection
CH-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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