Extended Data Fig. 4: Structural details of BI-3802-induced BCL6 filaments.

a, Density for BI-3802 in the 3.7-Å cryo-EM reconstruction. The crystal structure of BCL6 bound to BI-3802 (PDB 5MW2) was docked into the cryo-EM map and refined using phenix.real_space_refine. The cryo-EM density is shown in grey at a threshold of 0.0178 (from Chimera). b, Density of BI-3802 and key interacting residues (Arg28, Glu41, Tyr58, Cys84) for BCL6 polymerization. Each density in mesh is shown at a threshold of 0.0178 (from Chimera). c, d, Comparison of the cryo-EM model of polymerized BCL6 (white) with the BCL6 crystallographic lattice (yellow, PDB 5MW2) for dimer–dimer (c), and filament (d). e, Superimposed structures of BI-3802 (yellow) and BI-3812 (orange) bound to the BCL6 filament. BI-3812 was docked to the crystal structure of BCL6 BTB (PDB 5MW2), which was then aligned to the BI-3802-mediated BCL6 filament model. The solvent-exposed moiety of the inhibitor is clashing with the adjacent BCL6 dimer (grey). f, Preassembled 0.1 μM FITC-labelled BCoR peptide and 0.1 μM biotinylated BCL6(5–129) variants were treated with an increasing concentration of BI-3802, and the signal was measured by TR-FRET. The interaction of BCL6 with the BCOR co-repressor peptide was used to quantitively determine drug binding. Lines represent standard four-parameter log-logistic curve fit (n = 3).