SNAP annotations: PDB entry 1h9d

PDB-id

1h9d; DSSR-derived features in text and JSON formats; DNAproDB

Class

transcription factor

Method

X-ray (2.6 Å)

Summary

Aml1-cbf-beta-DNA complex

Reference

Bravo J, Li Z, Speck NA, Warren AJ (2001): "The Leukemia-Associated Aml1 (Runx1)-Cbfbeta Complex Functions as a DNA-Induced Molecular Clamp." Nat.Struct.Biol., 8, 371. doi: 10.1038/86264.

Abstract

We have determined the structure, at 2.6 A resolution, of the AML1 (Runx1) Runt domain--CBF beta--DNA ternary complex, the most common target for mutations in human leukemia. The structure reveals that the Runt domain DNA binding mechanism is unique within the p53 family of transcription factors. The extended C-terminal 'tail' and 'wing' elements adopt a specific DNA-bound conformation that clamps the phosphate backbone between the major and minor grooves of the distorted B-form DNA recognition site. Furthermore, the extended 'tail' mediates most of the NF-kappa B/Rel-like base-specific contacts in the major groove. The structure clearly explains the molecular basis for the loss of DNA binding function of the Runt domain--CBF beta complex as a consequence of the human disease-associated mutations in leukemogenesis and cleidocranial dysplasia.