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| | ==Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6== | | ==Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6== |
| - | <StructureSection load='5nwx' size='340' side='right' caption='[[5nwx]], [[Resolution|resolution]] 2.51Å' scene=''> | + | <StructureSection load='5nwx' size='340' side='right'caption='[[5nwx]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5nwx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NWX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nwx]] 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 crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NWX FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5nwm|5nwm]]</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]] 2.51Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=5nwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwx OCA], [https://pdbe.org/5nwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nwx RCSB], [https://www.ebi.ac.uk/pdbsum/5nwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwx ProSAT]</span></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=5nwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwx OCA], [http://pdbe.org/5nwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nwx RCSB], [http://www.ebi.ac.uk/pdbsum/5nwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCOA1_MOUSE NCOA1_MOUSE]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:8616895</ref> <ref>PMID:9506940</ref> <ref>PMID:12507421</ref> <ref>PMID:16148126</ref> [[http://www.uniprot.org/uniprot/STAT6_HUMAN STAT6_HUMAN]] Carries out a dual function: signal transduction and activation of transcription. Involved in interleukin-4 signalling. | + | [https://www.uniprot.org/uniprot/NCOA1_MOUSE NCOA1_MOUSE] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:8616895</ref> <ref>PMID:9506940</ref> <ref>PMID:12507421</ref> <ref>PMID:16148126</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone acetyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Becker, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Giller, K]] | + | [[Category: Mus musculus]] |
| - | [[Category: Griesinger, C]] | + | [[Category: Becker S]] |
| - | [[Category: Pfitzner, E]] | + | [[Category: Giller K]] |
| - | [[Category: Russo, L]] | + | [[Category: Griesinger C]] |
| - | [[Category: Ncoa1]] | + | [[Category: Pfitzner E]] |
| - | [[Category: Pas-b domain]] | + | [[Category: Russo L]] |
| - | [[Category: Stat6]]
| + | |
| - | [[Category: Transactivation domain]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
NCOA1_MOUSE Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.[1] [2] [3] [4]
Publication Abstract from PubMed
Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STAT6 with nuclear coactivator 1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite the availability of an X-ray structure of the PAS-B domain/ Leu(794)-Gly(814)-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1(257-385)/STAT6(783-814) complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6(783-814) peptide binds with additional N-terminal amino acids to NCoA1(257-385), compared to the STAT6(794-814) peptide, explaining its higher affinity. Secondary and tertiary structures existing in the free peptide are more highly populated in the complex, suggesting binding by conformational selection.
Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6.,Russo L, Giller K, Pfitzner E, Griesinger C, Becker S Sci Rep. 2017 Dec 4;7(1):16845. doi: 10.1038/s41598-017-17088-5. PMID:29203888[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403-14. PMID:8616895
- ↑ Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O'Malley BW. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science. 1998 Mar 20;279(5358):1922-5. PMID:9506940
- ↑ Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW, Chambon P, Auwerx J. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002 Dec 27;111(7):931-41. PMID:12507421
- ↑ Xie H, Sadim MS, Sun Z. RORgammat recruits steroid receptor coactivators to ensure thymocyte survival. J Immunol. 2005 Sep 15;175(6):3800-9. PMID:16148126
- ↑ Russo L, Giller K, Pfitzner E, Griesinger C, Becker S. Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6. Sci Rep. 2017 Dec 4;7(1):16845. doi: 10.1038/s41598-017-17088-5. PMID:29203888 doi:http://dx.doi.org/10.1038/s41598-017-17088-5
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