Comparative structural analysis of LSD1 and the LSD1-8a splice variant. A, Overall crystal structure of LSD1-8a–CoREST in complex with a histone peptide. LSD1-8a (residues 171-840) is in light blue, CoREST (residues 308-440) in red, and the histone H3 peptide (residues 1-16) in green. The FAD cofactor is in the orange ball-and-stick representation. The insertion site of E8a (residues Asp369A-Thr369B-Val369C-Lys369D) is highlighted. B, Close-up view of LSD1-8a structure at the site of exon E8a insertion. LSD1-8a structure is in blue, and it is superimposed onto native LSD1 (yellow; Protein Data Bank entry 2v1d) (Forneris et al., 2007). The orientation of the proteins is the same as in Figure 3A. The side chains of exon E8a residues are labeled in bold. Exon E8a insertion protrudes from the main body of the protein.