5HJB: Af9 Yeats In Complex With Histone H3 Crotonylation At K9

Recognition of histone covalent modifications by chromatin-binding protein modules ("readers") constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g., crotonylation, butyrylation, propionylation) have been recently identified, but readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyllysine over acetyllysine. Structural studies revealed an extended aromatic sandwiching cage with crotonyl specificity arising from pi-aromatic and hydrophobic interactions between crotonyl and aromatic rings. These features are conserved among the YEATS, but not the bromodomains. Using a cell-based model, we showed that AF9 co-localizes with crotonylated histone H3 and positively regulates gene expression in a YEATS domain-dependent manner. Our studies define the evolutionarily conserved YEATS domain as a family of crotonyllysine readers and specifically demonstrate that the YEATS domain of AF9 directly links histone crotonylation to active transcription.
PDB ID: 5HJBDownload
MMDB ID: 139053
PDB Deposition Date: 2016/1/12
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 5HJB: dimeric; determined by author and by software (PISA)
Molecular Components in 5HJB
Label Count Molecule
Proteins (2 molecules)
Protein Af-9(Gene symbol: MLLT3)
Molecule annotation
Peptide of Histone H3.1(Gene symbol: HIST1H3A)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB