Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4CRBN E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding ... position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Crystallography, X-Ray, DNA-Binding Proteins, Humans, Multiprotein Complexes, Protein Binding, Protein Conformation, Proteolysis, Substrate Specificity, Thalidomide, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitination
Adaptor Proteins, Signal Transducing, Crystallography, X-Ray, DNA-Binding Proteins, Humans, Multiprotein Complexes, Protein Binding, Protein Conformation, Proteolysis, Substrate Specificity, Thalidomide, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitination
Nat Struct Mol Biol
Date: Dec. 01, 2019
PubMed ID: 32251415
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