Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

15 Scopus Citations
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Author(s)

  • Yi Wang
  • Jing Jin
  • Matthew Wai Heng Chung
  • Quan Hao

Detail(s)

Original languageEnglish
Pages (from-to)2365-2370
Journal / PublicationProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number10
Online published20 Feb 2018
Publication statusPublished - 6 Mar 2018

Abstract

Lysine succinylation is a newly discovered posttranslational modification with distinctive physical properties. However, to date rarely have studies reported effectors capable of interpreting this modification on histones. Following our previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we identified the GAS41 YEATS domain as a reader of Ksuc on histones. Biochemical studies showed that the GAS41 YEATS domain presents significant binding affinity toward H3K122suc upon a protonated histidine residue. Furthermore, cellular studies showed that GAS41 had prominent interaction with H3K122suc on histones and also demonstrated the coenrichment of GAS41 and H3K122suc on the p21 promoter. To investigate the binding mechanism, we solved the crystal structure of the YEATS domain of Yaf9, the GAS41 homolog, in complex with an H3K122suc peptide that demonstrated the presence of a salt bridge formed when a protonated histidine residue (His39) recognizes the carboxyl terminal of the succinyl group. We also solved the apo structure of GAS41 YEATS domain, in which the conserved His43 residue superimposes well with His39 in the Yaf9 structure. Our findings identified a reader of succinyl-lysine, and the binding mechanism will provide insight into the development of specific regulators targeting GAS41.

Research Area(s)

  • GAS41, Reader, Succinyl-lysine

Citation Format(s)

Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation. / Wang, Yi; Jin, Jing; Chung, Matthew Wai Heng; Feng, Ling; Sun, Hongyan; Hao, Quan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 10, 06.03.2018, p. 2365-2370.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal