2A07: Crystal Structure Of Foxp2 Bound Specifically To Dna

FOXP (FOXP1-4) is a newly defined subfamily of the forkhead box (FOX) transcription factors. A mutation in the FOXP2 forkhead domain cosegregates with a severe speech disorder, whereas several mutations in the FOXP3 forkhead domain are linked to the IPEX syndrome in human and a similar autoimmune phenotype in mice. Here we report a 1.9 A crystal structure of the forkhead domain of human FOXP2 bound to DNA. This structure allows us to revise the previously proposed DNA recognition mechanism and provide a unifying model of DNA binding for the FOX family of proteins. Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer, made possible by a strategic substitution of a highly conserved proline in conventional FOX proteins with alanine in the P subfamily. Disease-causing mutations in FOXP2 and FOXP3 map either to the DNA binding surface or the domain-swapping dimer interface, functionally corroborating the crystal structure.
PDB ID: 2A07Download
MMDB ID: 86735
PDB Deposition Date: 2005/6/16
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2A07: decameric; determined by author
Molecular Components in 2A07
Label Count Molecule
Proteins (6 molecules)
Forkhead BOX Protein P2(Gene symbol: FOXP2)
Molecule annotation
Nucleotides(2 molecules)
5'- D(*ap*ap*cp*tp*ap*tp*gp*ap*ap*ap*cp*ap*ap*ap*tp*tp*tp*tp*cp *cp*t)-3'
Molecule annotation
5'- D(*tp*tp*ap*gp*gp*ap*ap*ap*ap*tp*tp*tp*gp*tp*tp*tp*cp*ap*tp *ap*g)-3'
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB