(a) Superposition of the Set1 catalytic domain (PDB: 6CHG, magenta) with MLL1 in different states (PDB: 5F6L, 5F5E, 2W5Y) showing different conformations of the SET-I helix. (b) Superposition of the Set1 catalytic domain (PDB: 6CHG, magenta) with MLL3 in different states (PDB: 5F6K chain C, E and 5F59) showing different conformations of the SET-I helix. (c) details of the SMART loop interactions with the SET-I helix of Set1 in COMPASS. The SMART loop in the crystal structure is colored orange and the SMART loop in the cryo-EM structure is colored tan.