Journal
BIOCHEMICAL JOURNAL
Volume 476, Issue -, Pages 211-223Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20180745
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Funding
- National Key Research and Development Program of China [2017YFA0503600, 2016YFA0400903]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [31621002]
- Major Research Plan of the National Natural Science Foundation of China [91853133]
- Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology [2017FXCX004]
- National Natural Science Foundation of China [U1532109, 31700671]
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Histone modification is a ubiquitous regulatory mechanism involved in a variety of biological processes, including gene expression, DNA damage repair, cell differentiation, and ontogenesis. Succinylation sites on histones have been identified and may have functional consequences. Here, we demonstrate that human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Structural studies of Sirt5 in complex with four succinyl peptides indicate an essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. Furthermore, biochemical assays reveal that the praline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Our findings illustrate the molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5 and provide insights for further studies of the biological functions associated with histone succinylation and Sirt5.
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