PDBsum entry 1puf

Transcription/DNA

PDB id: 1puf

Contents

Protein chains

77 a.a. *

73 a.a. *

DNA/RNA

Waters ×247

* Residue conservation analysis

PDB id:

1puf

Name:

Transcription/DNA

Title:

Crystal structure of hoxa9 and pbx1 homeodomains bound to DNA

Structure:

5'-d( Ap Cp Tp Cp Tp Ap Tp Gp Ap Tp Tp Tp Ap Cp Gp Ap Cp Gp Cp T)-3'. Chain: d. Engineered: yes. 5'-d( Tp Ap Gp Cp Gp Tp Cp Gp Tp Ap Ap Ap Tp Cp Ap Tp Ap Gp Ap G)-3'. Chain: e. Engineered: yes. Homeobox protein hox-a9.

Source:

Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Gene: hoxa9. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human.

Biol. unit:

Tetramer (from PQS)

Resolution:

1.90Å R-factor: 0.233 R-free: 0.268

Authors:

N.A.Laronde-Leblanc,C.Wolberger

Key ref:

N.A.LaRonde-LeBlanc and C.Wolberger (2003). Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. Genes Dev, 17, 2060-2072. PubMed id: 12923056

Date:

24-Jun-03 Release date: 02-Sep-03

Protein chain

P09631  (HXA9_MOUSE) -  Homeobox protein Hox-A9 from Mus musculus

Seq: 271 a.a.

Struc: 77 a.a.

Protein chain

P40424  (PBX1_HUMAN) -  Pre-B-cell leukemia transcription factor 1 from Homo sapiens

Seq: 430 a.a.

Struc: 73 a.a.

DNA/RNA chains

A-C-T-C-T-A-T-G-A-T-T-T-A-C-G-A-C-G-C-T 20 bases

T-A-G-C-G-T-C-G-T-A-A-A-T-C-A-T-A-G-A-G 20 bases

Genes Dev 17:2060-2072 (2003)

PubMed id: 12923056

Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior.

N.A.LaRonde-LeBlanc, C.Wolberger.

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.