SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.
Post-translational modifications (PTMs) regulate numerous proteins and are important for many biological processes. Lysine 4-oxononanoylation (4-ONylation) is a newly discovered histone PTM that prevents nucleosome assembly under oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from histones remains unknown, which hampers the further investigation of the cellular function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from histones and other proteins in live cells. A crystal structure of SIRT2 in complex with a 4-ONyl peptide reveals a lone pair-π interaction between Phe119 and the ketone oxygen of the 4-ONyl group. This is the first time that a mechanism to reverse 4-ONyl lysine modification is reported and will help to understand the role of SIRT2 in oxidative stress responses and the function of 4-ONylation.
School of Biomedical Science, University of Hong Kong , Hong Kong, China.
Jing
J
Jin
Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, National Engineering Research Center of Miao's Medicines, Guizhou Medical University , Guiyang, Guizhou 550004, China.
Bin
B
He
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Xiaoyu
X
Zhang
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Hening
H
Lin
School of Biomedical Science, University of Hong Kong , Hong Kong, China.
Yi
Y
Wang
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D056565:Sirtuin 2 / Q000737:chemistry / Q000378:metabolism*
D006657:Histones; D056565:Sirtuin 2; D008239:Lysine