Article

A Cryptic Interfacial Pocket Uncovered in Full CRL4 <sup>CRBN</sup> –IKZF3 Ubiquitylation Complex Enhances IMiD Efficacy

2025-06-09

Abstract excerpt

Immunomodulatory imide drugs (IMiDs) redirect the CUL4–RBX1–DDB1–CRBN (CRL4 CRBN ) ligase to ubiquitylate and degrade disease-linked proteins, but the full picture of how IMiDs glue the neosubstrate within the whole CRL4 CRBN complex remains unknown. We determined cryo-electron microscopy structures of eight approved or clinical IMiDs in full CRL4 CRBN ubiquitylation complexes at resolutions up to 3.4 Å, and re...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 88a23a89-340e-513d-9338-b98da5141b0d
DOI: 10.1101/2025.06.08.658527

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

A Cryptic Interfacial Pocket Uncovered in Full CRL4 <sup>CRBN</sup> –IKZF3 Ubiquitylation Complex Enhances IMiD EfficacyDOI 10.1101/2025.06.08.658527Read

Mining the CRBN Target Space Redefines Rules for Molecular Glue-induced Neosubstrate RecognitionSemantic proximity Read

Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settingsSemantic proximity Read

Molecular determinants underlying substrate receptor specificity of human CRL4B E3 ubiquitin ligaseSemantic proximity Read

Structural mimicry of UM171 and neomorphic cancer mutants co-opts E3 ligase KBTBD4 for HDAC1/2 recruitmentSemantic proximity Read

Integrated proteomic screening reveals design principles of CRBN molecular glue degradersSemantic proximity Read

Mapping the latent CRBN-molecular glue degrader interactomeSemantic proximity Read

Molecular surface mimicry enables CRBN to target G3BP2 for degradationSemantic proximity Read

GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular GluesSemantic proximity Read

IKZF1/3 and CRL4CRBN E3 ubiquitin ligase mutations and resistance to immunomodulatory drugs in multiple myelomaSemantic proximity Read

Design of a Cereblon construct for crystallographic and biophysical studies of protein degradersSemantic proximity Read

Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myelomaSemantic proximity Read

Engineering CRBN for rapid identification of next generation bindersSemantic proximity Read