FOXP2: Difference between revisions

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The forkhead domain of FOXP2 assumes unique <scene name='FOXP2/Opening_dimer/1'>dimeric</scene> and <scene name='FOXP2/Opening_monomer/1'>monomeric</scene> structures bound to [[DNA]]. The monomeric form binds more tightly to DNA and assumes the canonical winged-helix motif present in all the FOX proteins. The <scene name='FOXP2/Opening_monomer_structure/2'>structure consists</scene> of four alpha helices capped by a two stranded beta sheet. As is present in all FOX proteins, the turn between helices 2 and 3 contains <scene name='FOXP2/3-10/1'>a 3-10 helix</scene>. DNA recognition of FOXP2 is mediated by <scene name='FOXP2/Opening_monomer_helix_3/1'>helix 3</scene>. Residues Asn 550, Arg 553, His 554, Ser 557, and Leu 558 form strong <scene name='FOXP2/H3_binding/1'>hydrogen bonding and hydrophobic interactions</scene> with the DNA. Additionally, residues Tyr 509, Leu 527, Trp 573 and Tyr 531 also <scene name='FOXP2/H3_binding_additoins/1'>interact from other helices</scene>, wedging helix H3 within the <scene name='FOXP2/Major_groove/1'>major groove of the DNA</scene>. Perhaps unsurprisingly, Arg 553 is **conserved** among all forkhead proteins. In fact, mutation of Arg 533 to a histidine has been linked to the severe congenital speech disorders mentioned previously. Also of note, mutation of Ile 363 to a valine results in reduced binding to DNA and IPEX syndrome a disease causing T-cell dysfunction and subsequent autoimmunity.<ref>PMID:18481161</ref><ref name="Chen">PMID:16407075</ref>