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| | ==Crystal structure of human FLASH N-terminal domain== | | ==Crystal structure of human FLASH N-terminal domain== |
| - | <StructureSection load='6ano' size='340' side='right' caption='[[6ano]], [[Resolution|resolution]] 2.61Å' scene=''> | + | <StructureSection load='6ano' size='340' side='right'caption='[[6ano]], [[Resolution|resolution]] 2.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ano]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ANO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ANO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ano]] is a 2 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=6ANO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ANO FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.61Å</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=6ano FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ano OCA], [http://pdbe.org/6ano PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ano RCSB], [http://www.ebi.ac.uk/pdbsum/6ano PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ano ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=6ano FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ano OCA], [https://pdbe.org/6ano PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ano RCSB], [https://www.ebi.ac.uk/pdbsum/6ano PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ano ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/C8AP2_HUMAN C8AP2_HUMAN]] Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase.<ref>PMID:12477726</ref> <ref>PMID:15698540</ref> <ref>PMID:17003125</ref> <ref>PMID:17245429</ref> | + | [https://www.uniprot.org/uniprot/C8AP2_HUMAN C8AP2_HUMAN] Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase.<ref>PMID:12477726</ref> <ref>PMID:15698540</ref> <ref>PMID:17003125</ref> <ref>PMID:17245429</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: Aik, W S]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Tong, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Coiled-coil]] | + | [[Category: Aik WS]] |
| - | [[Category: Gene regulation]] | + | [[Category: Tong L]] |
| Structural highlights
Function
C8AP2_HUMAN Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase.[1] [2] [3] [4]
Publication Abstract from PubMed
Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3'-end by a mechanism distinct from cleavage and polyadenylation. They have a 3' stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.
The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing.,Aik WS, Lin MH, Tan D, Tripathy A, Marzluff WF, Dominski Z, Chou CY, Tong L PLoS One. 2017 Oct 11;12(10):e0186034. doi: 10.1371/journal.pone.0186034., eCollection 2017. PMID:29020104[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kino T, Chrousos GP. Tumor necrosis factor alpha receptor- and Fas-associated FLASH inhibit transcriptional activity of the glucocorticoid receptor by binding to and interfering with its interaction with p160 type nuclear receptor coactivators. J Biol Chem. 2003 Jan 31;278(5):3023-9. Epub 2002 Dec 10. PMID:12477726 doi:http://dx.doi.org/10.1074/jbc.M209234200
- ↑ Kino T, Ichijo T, Chrousos GP. FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors. J Steroid Biochem Mol Biol. 2004 Dec;92(5):357-63. Epub 2004 Dec 19. PMID:15698540 doi:http://dx.doi.org/S0960-0760(04)00374-7
- ↑ Barcaroli D, Bongiorno-Borbone L, Terrinoni A, Hofmann TG, Rossi M, Knight RA, Matera AG, Melino G, De Laurenzi V. FLASH is required for histone transcription and S-phase progression. Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14808-12. Epub 2006 Sep 26. PMID:17003125 doi:http://dx.doi.org/10.1073/pnas.0604227103
- ↑ Milovic-Holm K, Krieghoff E, Jensen K, Will H, Hofmann TG. FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies. EMBO J. 2007 Jan 24;26(2):391-401. PMID:17245429 doi:http://dx.doi.org/10.1038/sj.emboj.7601504
- ↑ Aik WS, Lin MH, Tan D, Tripathy A, Marzluff WF, Dominski Z, Chou CY, Tong L. The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing. PLoS One. 2017 Oct 11;12(10):e0186034. doi: 10.1371/journal.pone.0186034., eCollection 2017. PMID:29020104 doi:http://dx.doi.org/10.1371/journal.pone.0186034
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