Identification of SIRT3 as an eraser of H4K16la

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

Detail(s)

Original languageEnglish
Article number107757
Journal / PublicationiScience
Volume26
Issue number10
Online published28 Aug 2023
Publication statusPublished - 20 Oct 2023

Link(s)

Abstract

Lysine lactylation (Kla) is a novel histone post-translational modification discovered in late 2019. Later, HDAC1-3, were identified as the robust Kla erasers. While the Sirtuin family proteins showed weak eraser activities toward Kla, as reported. However, the catalytic mechanisms and physiological functions of HDACs and Sirtuins are not identical. In this study, we observed that SIRT3 exhibits a higher eraser activity against the H4K16la site than the other human Sirtuins. Crystal structures revealed the detailed binding mechanisms between lactyl-lysine peptides and SIRT3. Furthermore, a chemical probe, p-H4K16laAlk, was developed to capture potential Kla erasers from cell lysates. SIRT3 was captured by this probe and detected via proteomic analysis. And another chemical probe, p-H4K16la-NBD, was developed to detect the eraser-Kla delactylation processes directly via fluorescence indication. Our findings and chemical probes provide new directions for further investigating Kla and its roles in gene transcription regulation. © 2023 The Authors

Research Area(s)

  • Enzymology, Molecular interaction, Protein, Structural biology

Citation Format(s)

Identification of SIRT3 as an eraser of H4K16la. / Fan, Zhuming; Liu, Zhiyang; Zhang, Nan et al.
In: iScience, Vol. 26, No. 10, 107757, 20.10.2023.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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