6MIM

Crystal structure of AF9 YEATS domain Y78W mutant in complex with histone H3K9cr

Summary for 6MIM

• Entry DOI: 10.2210/pdb6mim/pdb
• Descriptor: Protein AF-9, Histone H3K9cr (3 entities in total)
• Functional Keywords: transcription, epigenetic, histone reader
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 35390.65

Authors

Vann, K.R.,Klein, B.J.,Kutateladze, T.G. (deposition date: 2018-09-19, release date: 2018-11-14, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.525 Å)