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. 2020 Apr;27(4):319-322.
doi: 10.1038/s41594-020-0405-9. Epub 2020 Apr 6.

Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex

Mary E Matyskiela  1 , Thomas Clayton  2 , Xinde Zheng  2 , Christopher Mayne  2 , Eileen Tran  2 , Aaron Carpenter  2 , Barbra Pagarigan  2 , Joseph McDonald  2 , Mark Rolfe  2 , Lawrence G Hamann  2 , Gang Lu  2 , Philip P Chamberlain  3
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Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex

Mary E Matyskiela et al. Nat Struct Mol Biol. 2020 Apr.

Abstract

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.

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References

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