5Y8V

Crystal structure of GAS41

Summary for 5Y8V

• Entry DOI: 10.2210/pdb5y8v/pdb
• Descriptor: YEATS domain-containing protein 4, MAGNESIUM ION (3 entities in total)
• Functional Keywords: yeats domain, nuclear protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : O95619
• Total number of polymer chains: 4
• Total formula weight: 66357.38

Authors

Wang, Y.,Hao, Q. (deposition date: 2017-08-21, release date: 2018-04-25, Last modification date: 2023-11-22)

Primary citation

Wang, Y.,Jin, J.,Chung, M.W.H.,Feng, L.,Sun, H.,Hao, Q.
Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation
Proc. Natl. Acad. Sci. U.S.A., 115:2365-2370, 2018

PubMed 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 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.

PubMed: 29463709
DOI: 10.1073/pnas.1717664115

Experimental method

X-RAY DIFFRACTION (2.61 Å)