7CFP

Crystal structure of WDR5 in complex with a H3Q5ser peptide

7CFP の概要

• エントリーDOI: 10.2210/pdb7cfp/pdb
• 分子名称: WD repeat-containing protein 5, H3Q5ser peptide, SEROTONIN, ... (4 entities in total)
• 機能のキーワード: complex, histone modification, reader, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38307.36

構造登録者

Zhao, J.,Zhang, X.,Zang, J. (登録日: 2020-06-27, 公開日: 2021-07-07, 最終更新日: 2024-11-06)

主引用文献

Zhao, J.,Chen, W.,Pan, Y.,Zhang, Y.,Sun, H.,Wang, H.,Yang, F.,Liu, Y.,Shen, N.,Zhang, X.,Mo, X.,Zang, J.
Structural insights into the recognition of histone H3Q5 serotonylation by WDR5.
Sci Adv, 7:-, 2021

PubMed Abstract: Serotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins that specifically recognize H3Q5ser remain unknown. Here, we found that WDR5 interacts with the N-terminal tail of histone H3 and functions as a "reader" for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that H3K4me3 modification is hampered upon disruption of WDR5-H3Q5ser interaction. WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes in neuroblastoma cells, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser-mediated epigenetic regulation apparently promotes tumorigenesis.

PubMed: 34144982
DOI: 10.1126/sciadv.abf4291

実験手法

X-RAY DIFFRACTION (1.6 Å)