121st General Meeting of the KCS

Type Oral Presentation
Area Oral Presentation for 2018 DOW Chemical Korea Award
Room No. Room 202A
Time THU 10:15-:
Code KCS.O-1
Subject A chemical biology route to site-specific authentic protein modifications
Authors Aerin Yang, Sura Ha, Jihye Ahn, Rira Kim, Sungyoon Kim, Younghoon Lee, Jaehoon Kim, Dieter Söll*, Hee-Yoon Lee*, Hee-Sung Park*
Korea Advanced Institute of Science and Technology, Korea
Abstract 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.
E-mail red88ar@kaist.ac.kr