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 Å 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. ©2006 Elsevier Ltd All rights reserved.
CITATION STYLE
Stroud, J. C., Wu, Y., Bates, D. L., Han, A., Nowick, K., Paabo, S., … Chen, L. (2006). Structure of the forkhead domain of FOXP2 bound to DNA. Structure, 14(1), 159–166. https://doi.org/10.1016/j.str.2005.10.005
Mendeley helps you to discover research relevant for your work.