Summary information and primary citation
- PDB-id
- 2a07; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription-DNA
- Method
- X-ray (1.9 Å)
- Summary
- Crystal structure of foxp2 bound specifically to DNA.
- Reference
- Stroud JC, Wu Y, Bates DL, Han A, Nowick K, Paabo S, Tong H, Chen L (2006): "Structure of the Forkhead Domain of FOXP2 Bound to DNA." Structure, 14, 159-166. doi: 10.1016/j.str.2005.10.005.
- Abstract
- 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.
