Fig. 2

Structural Basis of YEATS2 Recognition for Histone Acylation Marks. (A-D) Overall architecture of the YEATS domain (PDB: 7EIE) featuring a β-sheet core (color) and residue surface (gray). The aromatic cage (Y262/W282) accommodates diverse acyl groups, including Kac, Kbz, and Kcr. The H3K27ac, H3K27Kbz, and H3K27Kcr regions are represented by pink, blue, and orange, respectively. The data presented here show the YEATS domain of YEATS2 and its complex bound to Kac (PDB: 5XNV), Kbz (PDB: 6LSD) and Kcr (PDB: 5IQL). (E-F) Shared interactions include π-π stacking with Y262 and hydrophobic contacts with W282. The acetyl moiety nests within the hydrophobic pocket via Y262/W282 interactions, stabilized by S261 hydrogen bonding. The benzoyl group engages W282 through π-π stacking, with the “tip-sensor” S264 stabilizing the benzene ring. The crotonyl chain adopts a hook-like conformation, forming van der Waals contacts with F281/L259. Structural alignment (RMSD < 1.2 Å) highlights sidechain plasticity rather than global rearrangements during acyl group adaptation. The structure framework is adapted from Mi et al., [27], Ren et al., [26], and Zhao et al., [23]. H3, Histone H3; K, Lysine; ac, Acetylation; cr, Crotonylation; bz, Benzoylation