Fig. 3: Cryo-EM structures of inhibited BRISC dimers.
From: Molecular glues that inhibit deubiquitylase activity and inflammatory signaling
a, Cryo-EM density map of BRISC–FX-171-C costructure at 3.0 Å. BRISC monomers are shown as gray and salmon cartoon models and fitted to the cryo-EM map shown as a transparent surface at a 0.00224 threshold. The C termini of BRCC45 (residues 275–383) and MERIT40 are rigid-body fitted into the density. b, BRISC–FX-171-C cryo-EM density map at a 0.0165 threshold. BRISC subunits are colored by chain. The density corresponding to FX-171-C is colored orange and highlighted in orange boxes. The maps shown in a–c are locally filtered maps generated using RELION local resolution estimation. c, Close-up views of the indicated inhibitor density comparing binding sites for FX-171-C (left) and JMS-175-2 (right). d, Cryo-EM density at the equivalent sites of BRCC36, Abraxas 2 and BRCC45′ in the BRISC–FX-171-C costructure, where there is no dimer interface and no additional density corresponding to FX-171-C. The maps in a–d had dust cleaning (size 7.1) applied in ChimeraX. e, Structures of FX-171-C and JMS-175-2 modeled in state 1 and state 2. Cryo-EM density of the inhibitor after focused refinement represented as a mesh and displayed using the surface zone tool (FX-171-C, radius = 2.6; JMS-175-2, radius = 2.2) in ChimeraX.
