Extended Data Fig. 5: Structural comparison of WT LC and Y391K LC in complex with H3K4M and H3K4M/K14ac peptides.
From: Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1
The active site of LC with the peptides is magnified (top), highlighting key residues and CoREST1′s conformation in proximity. (a) WT LC H3K4M vs. H3K4M/K14ac: In the H3K4M/K14ac structure, K9* of H3K4M/K14ac (brown) forms a compensatory salt bridge with E559LSD1 due to K14 acetylation. (b) WT LC H3K4M vs. Y391K LC H3K4M: CoREST1, bound to Y391K LSD1 (black), adopts a distinct conformation compared to CoREST1 bound to WT LSD1 (blue), shifting downward towards H3K4M. This shift is caused by the charge repulsion from K391LSD1. (c) Y391K LC H3K4M vs. Y391K H3K4M/K14ac: In both structures, K9 of H3K4M (orange) and K9** of H3K4M/K14ac (light purple) are situated nearby H564LSD1 Q358LSD1, without forming a compensatory salt bridge with E559LSD1. CoREST1 conformation remains downward, as described in (b). (d) Y391K LC H3K4M/K14ac vs. WT LC H3K4M/K14ac: In the WT LC structure, K9* of H3K4M/K14ac makes a compensatory salt bridge with E559LSD1, whereas in the Y391K LC structure, K9** of H3K4M/K14ac remains unchanged, residing nearby H564LSD1 and Q358LSD1. Note: * and ** represent different lysine residues in the H3K4M and H3K4M/K14ac peptides, respectively.
