2A07

Crystal Structure of Foxp2 bound Specifically to DNA.

Summary for 2A07

• Entry DOI: 10.2210/pdb2a07/pdb
• Descriptor: 5'-D(*AP*AP*CP*TP*AP*TP*GP*AP*AP*AP*CP*AP*AP*AP*TP*TP*TP*TP*CP*CP*T)-3', 5'-D(*TP*TP*AP*GP*GP*AP*AP*AP*AP*TP*TP*TP*GP*TP*TP*TP*CP*AP*TP*AP*G)-3', Forkhead box protein P2, ... (5 entities in total)
• Functional Keywords: forkhead, double-helix, swapping, homodimer, monomer, winged-helix, magnesium, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : O15409
• Total number of polymer chains: 10
• Total formula weight: 92060.44

Authors

Stroud, J.C.,Wu, Y.,Bates, D.L.,Han, A.,Nowick, K.,Paabo, S.,Tong, H.,Chen, L. (deposition date: 2005-06-16, release date: 2006-01-31, Last modification date: 2024-02-14)

Primary citation

Stroud, J.C.,Wu, Y.,Bates, D.L.,Han, A.,Nowick, K.,Paabo, S.,Tong, H.,Chen, L.
Structure of the Forkhead Domain of FOXP2 Bound to DNA.
Structure, 14:159-166, 2006

PubMed 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.

PubMed: 16407075
DOI: 10.1016/j.str.2005.10.005

Experimental method

X-RAY DIFFRACTION (1.9 Å)