6MIP

Crystal structure of Taf14 YEATS domain G82A mutant

6MIP の概要

• エントリーDOI: 10.2210/pdb6mip/pdb
• 分子名称: Transcription initiation factor TFIID subunit 14, DI(HYDROXYETHYL)ETHER (3 entities in total)
• 機能のキーワード: transcription, epigenetic, histone reader
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16300.64

構造登録者

Klein, B.J.,Andrews, F.H.,Kutateladze, T.G. (登録日: 2018-09-19, 公開日: 2018-11-14, 最終更新日: 2023-10-11)

主引用文献

Klein, B.J.,Vann, K.R.,Andrews, F.H.,Wang, W.W.,Zhang, J.,Zhang, Y.,Beloglazkina, A.A.,Mi, W.,Li, Y.,Li, H.,Shi, X.,Kutateladze, A.G.,Strahl, B.D.,Liu, W.R.,Kutateladze, T.G.
Structural insights into the pi-pi-pi stacking mechanism and DNA-binding activity of the YEATS domain.
Nat Commun, 9:4574-4574, 2018

PubMed Abstract: The YEATS domain has been identified as a reader of histone acylation and more recently emerged as a promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for π-π-π stacking involving the YEATS domains of yeast Taf14 and human AF9 and acylated histone H3 peptides and explore DNA-binding activities of these domains. Taf14-YEATS selects for crotonyllysine, forming π stacking with both the crotonyl amide and the alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated and unsaturated acyllysines, engaging them through π stacking with the acyl amide. Importantly, AF9-YEATS is capable of binding to DNA, whereas Taf14-YEATS is not. Using a structure-guided approach, we engineered a mutant of Taf14-YEATS that engages crotonyllysine through the aromatic-aliphatic-aromatic π stacking and shows high selectivity for the crotonyl H3K9 modification. Our findings shed light on the molecular principles underlying recognition of acyllysine marks and reveal a previously unidentified DNA-binding activity of AF9-YEATS.

PubMed: 30385749
DOI: 10.1038/s41467-018-07072-6

実験手法

X-RAY DIFFRACTION (2 Å)