PDBsum entry 1lfu

Transcription

PDB id: 1lfu

Contents

Protein chain

82 a.a. *

DNA/RNA

* Residue conservation analysis

PDB id:

1lfu

Name:

Transcription

Title:

Nmr solution structure of the extended pbx homeodomain bound to DNA

Structure:

5'-d( Gp Cp Gp Cp Ap Tp Gp Ap Tp Tp Gp Cp Cp C)-3'. Chain: a. Engineered: yes. 5'-d( Gp Gp Gp Cp Ap Ap Tp Cp Ap Tp Gp Cp Gp C)-3'. Chain: b. Engineered: yes. Homeobox protein pbx1. Chain: p. Fragment: homeodomain and conserved c-terminus.

Source:

Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Gene: pbx1. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

T.Sprules,N.Green,M.Featherstone,K.Gehring

Key ref:

T.Sprules et al. (2003). Lock and key binding of the HOX YPWM peptide to the PBX homeodomain. J Biol Chem, 278, 1053-1058. PubMed id: 12409300 DOI: 10.1074/jbc.M207504200

Date:

12-Apr-02 Release date: 14-Jan-03

Protein chain

P41778  (PBX1_MOUSE) -  Pre-B-cell leukemia transcription factor 1 from Mus musculus

Seq: 430 a.a.

Struc: 82 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains

G-C-G-C-A-T-G-A-T-T-G-C-C-C 14 bases

G-G-G-C-A-A-T-C-A-T-G-C-G-C 14 bases

DOI no: 10.1074/jbc.M207504200

J Biol Chem 278:1053-1058 (2003)

PubMed id: 12409300

Lock and key binding of the HOX YPWM peptide to the PBX homeodomain.

T.Sprules, N.Green, M.Featherstone, K.Gehring.

ABSTRACT

HOX homeodomain proteins bind short core DNA sequences to control very specific developmental processes. DNA binding affinity and sequence selectivity are increased by the formation of cooperative complexes with the PBX homeodomain protein. A conserved YPWM motif in the HOX protein is necessary for cooperative binding with PBX. We have determined the structure of a PBX homeodomain bound to a 14-mer DNA duplex. A relaxation-optimized procedure was developed to measure DNA residual dipolar couplings at natural abundance in the 20-kDa binary complex. When the PBX homeodomain binds to DNA, a fourth alpha-helix is formed in the homeodomain. This helix rigidifies the DNA recognition helix of PBX and forms a hydrophobic binding site for the HOX YPWM peptide. The HOX peptide itself shows some structure in solution and suggests that the interaction between PBX and HOX is an example of "lock and key" binding. The NMR structure explains the requirement of DNA for the PBX-HOX interaction and the increased affinity of DNA binding.

Selected figure(s)

Figure 2.
Fig. 2. The structure of the PBX-DNA complex. Superposition of the heavy atoms of the 20 lowest energy structures of the extended PBX homeodomain bound to a 14-mer DNA duplex. The backbone of PBX residues 1-72 and the DNA duplex are illustrated. The N terminus of the protein is labeled N; C indicates the position of amino acid 72. Base pair 1 of the DNA is shown at the bottom of the figure.

Figure 5.
Fig. 5. Binding of the HOXA1 peptide to the PBX-DNA complex. a, superposition of the 15N-HSQC of the free (black) and bound (gray) HOXA1 peptide. Spectra recorded at 25 °C and 500 MHz. b, schematic representation of chemical shift changes on binding to the PBX-DNA complex. HN = (( H[bound] H[free] × 5)2 + ( N[bound] N[free])2). c, heteronuclear NOEs. The ratio of the saturated versus unsaturated experiment plotted by residue.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 1053-1058) copyright 2003.

Figures were selected by the author.