Extended Data Fig. 5: CDK12 contacts residues on DDB1 that are otherwise involved in DCAF binding.
From: The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K
a, Structure of the DDB1(ΔBPB)–(R)-CR8–CDK12 complex. The CDK12 C-terminal extension binds a cleft between the DDB1 BPA and BPC domains (arrow) and adopts an helix–loop–helix (HLH)-like fold. b, Diverse DCAFs bind DDB1 through HLH or HLH-like folds. c, Sequence alignment of identically positioned helices of different HLH domains. d, Overview of protein–protein interaction hotspots. e, Counter-titration of unlabelled wild-type or mutant DDB1 (0–10 μM) into the preassembled DDB1terbium–CR8–CDK12–cyclin KAlexa488 complex (n = 3). f, Counter-titration of unlabelled wild-type or mutant DDB1 (0–10 μM) into the preassembled DDB1terbium–CR8–CDK12–cyclin KAlexa488 complex (n = 3). g–i, Close-up views of DDB1 residues contacted by CDK12 (top) that are otherwise involved in DCAF binding (bottom).
