|
|
| Line 1: |
Line 1: |
| | | | |
| | ==NMR structure of the CBP-TAZ1/STAT2-TAD complex== | | ==NMR structure of the CBP-TAZ1/STAT2-TAD complex== |
| - | <StructureSection load='2ka4' size='340' side='right'caption='[[2ka4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2ka4' size='340' side='right'caption='[[2ka4]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ka4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KA4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ka4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KA4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ka6|2ka6]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Crebbp ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), STAT2 ([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=2ka4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ka4 OCA], [https://pdbe.org/2ka4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ka4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ka4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ka4 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=2ka4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ka4 OCA], [https://pdbe.org/2ka4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ka4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ka4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ka4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/STAT2_HUMAN STAT2_HUMAN]] Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.<ref>PMID:9020188</ref>
| + | [https://www.uniprot.org/uniprot/CBP_MOUSE CBP_MOUSE] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).<ref>PMID:10207073</ref> <ref>PMID:11701890</ref> <ref>PMID:15220471</ref> <ref>PMID:16287980</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 37: |
Line 36: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dyson, H J]] | + | [[Category: Dyson HJ]] |
| - | [[Category: Martinez-Yamout, M A]] | + | [[Category: Martinez-Yamout MA]] |
| - | [[Category: Wojciak, J M]] | + | [[Category: Wojciak JM]] |
| - | [[Category: Wright, P E]] | + | [[Category: Wright PE]] |
| - | [[Category: Activator]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Antiviral defense]]
| + | |
| - | [[Category: Bromodomain]]
| + | |
| - | [[Category: Cbp/p300]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Stat2]]
| + | |
| - | [[Category: Taz1]]
| + | |
| - | [[Category: Transactivation domain]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Transcription regulator]]
| + | |
| Structural highlights
Function
CBP_MOUSE Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).[1] [2] [3] [4]
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
CBP/p300 transcriptional coactivators mediate gene expression by integrating cellular signals through interactions with multiple transcription factors. To elucidate the molecular and structural basis for CBP-dependent gene expression, we determined structures of the CBP TAZ1 and TAZ2 domains in complex with the transactivation domains (TADs) of signal transducer and activator of transcription 2 (STAT2) and STAT1, respectively. Despite the topological similarity of the TAZ1 and TAZ2 domains, subtle differences in helix packing and surface grooves constitute major determinants of target selectivity. Our results suggest that TAZ1 preferentially binds long TADs capable of contacting multiple surface grooves simultaneously, whereas smaller TADs that are restricted to a single contiguous binding surface form complexes with TAZ2. Complex formation for both STAT TADs involves coupled folding and binding, driven by intermolecular hydrophobic and electrostatic interactions. Phosphorylation of S727, required for maximal transcriptional activity of STAT1, does not enhance binding to any of the CBP domains. Because the different STAT TADs recognize different regions of CBP/p300, there is a potential for multivalent binding by STAT heterodimers that could enhance the recruitment of the coactivators to promoters.
Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains.,Wojciak JM, Martinez-Yamout MA, Dyson HJ, Wright PE EMBO J. 2009 Apr 8;28(7):948-58. Epub 2009 Feb 12. PMID:19214187[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hung HL, Lau J, Kim AY, Weiss MJ, Blobel GA. CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Mol Cell Biol. 1999 May;19(5):3496-505. PMID:10207073
- ↑ Xu W, Chen H, Du K, Asahara H, Tini M, Emerson BM, Montminy M, Evans RM. A transcriptional switch mediated by cofactor methylation. Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8. PMID:11701890 doi:10.1126/science.1065961
- ↑ Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T, Fukamizu A. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10042-7. Epub 2004 Jun 25. PMID:15220471 doi:10.1073/pnas.0400593101
- ↑ Kuo HY, Chang CC, Jeng JC, Hu HM, Lin DY, Maul GG, Kwok RP, Shih HM. SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16973-8. Epub 2005 Nov 15. PMID:16287980 doi:10.1073/pnas.0504460102
- ↑ Wojciak JM, Martinez-Yamout MA, Dyson HJ, Wright PE. Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains. EMBO J. 2009 Apr 8;28(7):948-58. Epub 2009 Feb 12. PMID:19214187 doi:10.1038/emboj.2009.30
|
