1PUF

Crystal Structure of HoxA9 and Pbx1 homeodomains bound to DNA

1PUF の概要

• エントリーDOI: 10.2210/pdb1puf/pdb
• 分子名称: 5'-D(*AP*CP*TP*CP*TP*AP*TP*GP*AP*TP*TP*TP*AP*CP*GP*AP*CP*GP*CP*T)-3', 5'-D(*TP*AP*GP*CP*GP*TP*CP*GP*TP*AP*AP*AP*TP*CP*AP*TP*AP*GP*AP*G)-3', Homeobox protein Hox-A9, ... (5 entities in total)
• 機能のキーワード: homeodomian, protein-dna complex, hox hexapeptide, tale homeodomain, homeodomain interaction, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Nucleus: P09631; Nucleus (Probable): P40424
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 30660.19

構造登録者

Laronde-Leblanc, N.A.,Wolberger, C. (登録日: 2003-06-24, 公開日: 2003-09-02, 最終更新日: 2023-08-16)

主引用文献

LARONDE-LEBLANC, N.A.,Wolberger, C.
STRUCTURE OF HOXA9 AND PBX1 BOUND TO DNA: HOX HEXAPEPTIDE AND DNA RECOGNITION ANTERIOR TO POSTERIOR
Genes Dev., 17:2060-2072, 2003

PubMed Abstract: The HOX/HOM superfamily of homeodomain proteins controls cell fate and segmental embryonic patterning by a mechanism that is conserved in all metazoans. The linear arrangement of the Hox genes on the chromosome correlates with the spatial distribution of HOX protein expression along the anterior-posterior axis of the embryo. Most HOX proteins bind DNA cooperatively with members of the PBC family of TALE-type homeodomain proteins, which includes human Pbx1. Cooperative DNA binding between HOX and PBC proteins requires a residue N-terminal to the HOX homeodomain termed the hexapeptide, which differs significantly in sequence between anterior- and posterior-regulating HOX proteins. We report here the 1.9-A-resolution structure of a posterior HOX protein, HoxA9, complexed with Pbx1 and DNA, which reveals that the posterior Hox hexapeptide adopts an altered conformation as compared with that seen in previously determined anterior HOX/PBC structures. The additional nonspecific interactions and altered DNA conformation in this structure account for the stronger DNA-binding affinity and altered specificity observed for posterior HOX proteins when compared with anterior HOX proteins. DNA-binding studies of wild-type and mutant HoxA9 and HoxB1 show residues in the N-terminal arm of the homeodomains are critical for proper DNA sequence recognition despite lack of direct contact by these residues to the DNA bases. These results help shed light on the mechanism of transcriptional regulation by HOX proteins and show how DNA-binding proteins may use indirect contacts to determine sequence specificity.

PubMed: 12923056
DOI: 10.1101/gad.1103303

実験手法

X-RAY DIFFRACTION (1.9 Å)