2as5

From Proteopedia

(Difference between revisions)

Current revision

Structure of the DNA binding domains of NFAT and FOXP2 bound specifically to DNA.

Structural highlights

2as5 is a 8 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 2.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NFAC2_HUMAN Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.^[1]

Evolutionary Conservation

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

Publication Abstract from PubMed

Antigen stimulation of immune cells activates the transcription factor NFAT, a key regulator of T cell activation and anergy. NFAT forms cooperative complexes with the AP-1 family of transcription factors and regulates T cell activation-associated genes. Here we show that regulatory T cell (Treg) function is mediated by an analogous cooperative complex of NFAT with the forkhead transcription factor FOXP3, a lineage specification factor for Tregs. The crystal structure of an NFAT:FOXP2:DNA complex reveals an extensive protein-protein interaction interface between NFAT and FOXP2. Structure-guided mutations of FOXP3, predicted to progressively disrupt its interaction with NFAT, interfere in a graded manner with the ability of FOXP3 to repress expression of the cytokine IL2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function in a murine model of autoimmune diabetes. Thus by switching transcriptional partners, NFAT converts the acute T cell activation program into the suppressor program of Tregs.

FOXP3 controls regulatory T cell function through cooperation with NFAT.,Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D, Benoist C, Chen L, Rao A Cell. 2006 Jul 28;126(2):375-87. PMID:16873067^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yiu GK, Kaunisto A, Chin YR, Toker A. NFAT promotes carcinoma invasive migration through glypican-6. Biochem J. 2011 Nov 15;440(1):157-66. doi: 10.1042/BJ20110530. PMID:21871017 doi:10.1042/BJ20110530
↑ Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D, Benoist C, Chen L, Rao A. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006 Jul 28;126(2):375-87. PMID:16873067 doi:10.1016/j.cell.2006.05.042

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2as5"

@@ Line 3: / Line 3: @@
 <StructureSection load='2as5' size='340' side='right'caption='[[2as5]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2as5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AS5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2as5]] is a 8 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=2AS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AS5 FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a02|1a02]], [[1owr|1owr]], [[2a07|2a07]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NFATC2, NFAT1, NFATP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FOXP2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2as5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2as5 OCA], [https://pdbe.org/2as5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2as5 RCSB], [https://www.ebi.ac.uk/pdbsum/2as5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2as5 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[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 ==
-[[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. [[https://www.uniprot.org/uniprot/NFAC2_HUMAN NFAC2_HUMAN]] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.<ref>PMID:21871017</ref>
+[https://www.uniprot.org/uniprot/NFAC2_HUMAN NFAC2_HUMAN] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.<ref>PMID:21871017</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bates, D L]]
+[[Category: Bates DL]]
-[[Category: Borde, M]]
+[[Category: Borde M]]
-[[Category: Chen, L]]
+[[Category: Chen L]]
-[[Category: Guo, L]]
+[[Category: Guo L]]
-[[Category: Han, A]]
+[[Category: Han A]]
-[[Category: Rao, A]]
+[[Category: Rao A]]
-[[Category: Stroud, J C]]
+[[Category: Stroud JC]]
-[[Category: Wu, Y]]
+[[Category: Wu Y]]
-[[Category: B-dna]]
-[[Category: Forkhead domain]]
-[[Category: Ig fold]]
-[[Category: Rel homology region]]
-[[Category: Rhr domain]]
-[[Category: Transcription-dna complex]]
-[[Category: Winged helix-turn-helix]]

2as5

From Proteopedia

Current revision

Structure of the DNA binding domains of NFAT and FOXP2 bound specifically to DNA.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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