Fig. 5: Cryo-EM structure of the KBTBD4R313PRR-HDAC2 complex reveals the basis of neomorphic substrate recruitment in cancer. | Nature Communications

Fig. 5: Cryo-EM structure of the KBTBD4R313PRR-HDAC2 complex reveals the basis of neomorphic substrate recruitment in cancer.

From: Structural mimicry of UM171 and neomorphic cancer mutants co-opts E3 ligase KBTBD4 for HDAC1/2 recruitment

Fig. 5: Cryo-EM structure of the KBTBD4R313PRR-HDAC2 complex reveals the basis of neomorphic substrate recruitment in cancer.The alternative text for this image may have been generated using AI.

a Ribbon representation of the KBTBD4R313PRR Kelch domain. The Kelch β-propeller consists of blades I to VI with each blade consisting of four antiparallel β strands (labelled A-D). Loops connecting βB and βB in blade II and IV are labelled as BC II and BC IV, respectively. The R313PRR cancer mutation in BC II is shown as red spheres. b Ribbon representation of HDAC2 binding to KBTBD4R313PRR_a at site 1 (BC II) and KBTBD4R313PRR_b at site 2 (BC IV). The second HDAC2 chain in the model is a symmetric duplication of the first and, therefore, not shown for simplicity. c Close-up view of site 1 interface. HDAC2 is shown as yellow surface and KBTBD4R313PRR_a as cyan ribbon. The key interacting arginine residues in KBTBD4R313PRR_a are shown as sticks in cyan. d–f Close-up views of site 1 key interfacial residues shown in sticks with the same colour scheme as c. Hydrogen bonding is indicated by dashed lines. g Close-up view of the site 2 interface. HDAC2 is shown as yellow surface and KBTBD4R313PRR_b as grey ribbon. The key interacting residues in KBTBD4R313PRR are shown as grey sticks. h–j Close-up views of site 2. Key interfacial residues are shown in sticks with the same colour scheme as in g.

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