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==Crystal Structure of Foxp2 bound Specifically to DNA.==
==Crystal Structure of Foxp2 bound Specifically to DNA.==
<StructureSection load='2a07' size='340' side='right' caption='[[2a07]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='2a07' size='340' side='right'caption='[[2a07]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a07]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A07 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2a07]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A07 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOXP2, CAGH44, TNRC10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a07 OCA], [http://pdbe.org/2a07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a07 RCSB], [http://www.ebi.ac.uk/pdbsum/2a07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a07 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2a07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a07 OCA], [https://pdbe.org/2a07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a07 RCSB], [https://www.ebi.ac.uk/pdbsum/2a07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a07 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/FOXP2_HUMAN FOXP2_HUMAN]] Defects in FOXP2 are the cause of speech-language disorder 1 (SPCH1) [MIM:[http://omim.org/entry/602081 602081]]; also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Affected individuals have a severe impairment in the selection and sequencing of fine orofacial movements, which are necessary for articulation. They also show deficits in several facets of language processing (such as the ability to break up words into their constituent phonemes) and grammatical skills.<ref>PMID:11586359</ref>  Note=A chromosomal aberration involving FOXP2 is a cause of severe speech and language impairment. Translocation t(5;7)(q22;q31.2).  
[https://www.uniprot.org/uniprot/FOXP2_HUMAN FOXP2_HUMAN] Defects in FOXP2 are the cause of speech-language disorder 1 (SPCH1) [MIM:[https://omim.org/entry/602081 602081]; also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Affected individuals have a severe impairment in the selection and sequencing of fine orofacial movements, which are necessary for articulation. They also show deficits in several facets of language processing (such as the ability to break up words into their constituent phonemes) and grammatical skills.<ref>PMID:11586359</ref>  Note=A chromosomal aberration involving FOXP2 is a cause of severe speech and language impairment. Translocation t(5;7)(q22;q31.2).
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/FOXP2_HUMAN FOXP2_HUMAN]] Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Involved in neural mechanisms mediating the development of speech and language.  
[https://www.uniprot.org/uniprot/FOXP2_HUMAN FOXP2_HUMAN] Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Involved in neural mechanisms mediating the development of speech and language.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a07 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a07 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
Structure of the forkhead domain of FOXP2 bound to DNA.,Stroud JC, Wu Y, Bates DL, Han A, Nowick K, Paabo S, Tong H, Chen L Structure. 2006 Jan;14(1):159-66. PMID:16407075<ref>PMID:16407075</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a07" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[FOXP2|FOXP2]]
*[[FOX 3D structures|FOX 3D structures]]
*[[Forkhead box protein|Forkhead box protein]]
*[[Foxp2 bound specifically to DNA|Foxp2 bound specifically to DNA]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Bates, D L]]
[[Category: Large Structures]]
[[Category: Chen, L]]
[[Category: Bates DL]]
[[Category: Han, A]]
[[Category: Chen L]]
[[Category: Nowick, K]]
[[Category: Han A]]
[[Category: Paabo, S]]
[[Category: Nowick K]]
[[Category: Stroud, J C]]
[[Category: Paabo S]]
[[Category: Tong, H]]
[[Category: Stroud JC]]
[[Category: Wu, Y]]
[[Category: Tong H]]
[[Category: Double-helix]]
[[Category: Wu Y]]
[[Category: Forkhead]]
[[Category: Homodimer]]
[[Category: Magnesium]]
[[Category: Monomer]]
[[Category: Swapping]]
[[Category: Transcription-dna complex]]
[[Category: Winged-helix]]

Latest revision as of 12:10, 14 February 2024

Crystal Structure of Foxp2 bound Specifically to DNA.Crystal Structure of Foxp2 bound Specifically to DNA.

Structural highlights

2a07 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FOXP2_HUMAN Defects in FOXP2 are the cause of speech-language disorder 1 (SPCH1) [MIM:602081; also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Affected individuals have a severe impairment in the selection and sequencing of fine orofacial movements, which are necessary for articulation. They also show deficits in several facets of language processing (such as the ability to break up words into their constituent phonemes) and grammatical skills.[1] Note=A chromosomal aberration involving FOXP2 is a cause of severe speech and language impairment. Translocation t(5;7)(q22;q31.2).

Function

FOXP2_HUMAN Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Involved in neural mechanisms mediating the development of speech and language.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature. 2001 Oct 4;413(6855):519-23. PMID:11586359 doi:10.1038/35097076

2a07, resolution 1.90Å

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