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<StructureSection load='5fb1' size='340' side='right'caption='[[5fb1]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='5fb1' size='340' side='right'caption='[[5fb1]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5fb1]] is a 2 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=5FB1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FB1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5fb1]] 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=5FB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FB1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <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">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fb0|5fb0]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SP100 ([http://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=5fb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fb1 OCA], [https://pdbe.org/5fb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fb1 RCSB], [https://www.ebi.ac.uk/pdbsum/5fb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fb1 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fb1 OCA], [http://pdbe.org/5fb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fb1 RCSB], [http://www.ebi.ac.uk/pdbsum/5fb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fb1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SP100_HUMAN SP100_HUMAN]] Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation.<ref>PMID:11909962</ref> <ref>PMID:14647468</ref> <ref>PMID:15247905</ref> <ref>PMID:15592518</ref> <ref>PMID:15767676</ref> <ref>PMID:16177824</ref> <ref>PMID:17245429</ref> <ref>PMID:21274506</ref> <ref>PMID:21880768</ref> 
[https://www.uniprot.org/uniprot/SP100_HUMAN SP100_HUMAN] Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation.<ref>PMID:11909962</ref> <ref>PMID:14647468</ref> <ref>PMID:15247905</ref> <ref>PMID:15592518</ref> <ref>PMID:15767676</ref> <ref>PMID:16177824</ref> <ref>PMID:17245429</ref> <ref>PMID:21274506</ref> <ref>PMID:21880768</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The decoding of histone post-translational modifications by chromatin-binding modules ("readers") constitutes one major mechanism of epigenetic regulation. Nuclear antigen Sp100 (SPECKLED, 100 kDa), a constitutive component of the promyelocytic leukemia nuclear bodies, plays key roles in intrinsic immunity and transcriptional repression. Sp100C, a splicing isoform specifically up-regulated upon interferon stimulation, harbors a unique tandem plant homeodomain (PHD) finger and bromodomain at its C terminus. Combining structural, quantitative binding, and cellular co-localization studies, we characterized Sp100C PHD finger as an unmethylated histone H3 Lys(4) (H3K4me0) reader that tolerates histone H3 Thr(3) phosphorylation (H3T3ph), histone H3 Lys(9) trimethylation (H3K9me3), and histone H3 Ser(10) phosphorylation (H3S10ph), hallmarks associated with the mitotic chromosome. In contrast, whereas H3K4me0 reader activity is conserved in Sp140, an Sp100C paralog, the multivalent tolerance of H3T3ph, H3K9me3, and H3S10ph was lost for Sp140. The complex structure determined at 2.1 A revealed a highly coordinated lysine -amine recognition sphere formed by an extended N-terminal motif for H3K4me0 readout. Interestingly, reader pocket rigidification by disulfide bond formation enhanced H3K4me0 binding by Sp100C. An additional complex structure solved at 2.7 A revealed that H3T3ph is recognized by the arginine residue, Arg(713), that is unique to the PHD finger of Sp100C. Consistent with a restrictive cellular role of Sp100C, these results establish a direct chromatin targeting function of Sp100C that may regulate transcriptional gene silencing and promyelocytic leukemia nuclear body-mediated intrinsic immunity in response to interferon stimulation.
 
Multifaceted Histone H3 Methylation and Phosphorylation Readout by the Plant Homeodomain Finger of Human Nuclear Antigen Sp100C.,Zhang X, Zhao D, Xiong X, He Z, Li H J Biol Chem. 2016 Jun 10;291(24):12786-98. doi: 10.1074/jbc.M116.721159. Epub, 2016 Apr 22. PMID:27129259<ref>PMID:27129259</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fb1" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Li, H]]
[[Category: Li H]]
[[Category: Zhang, X]]
[[Category: Zhang X]]
[[Category: Bromodomain]]
[[Category: Transcription-structural protein complex]]
[[Category: Zinc finger protein]]

Latest revision as of 12:11, 20 March 2024

Crystal Structure of a PHD finger bound to histone H3 K9me3 peptideCrystal Structure of a PHD finger bound to histone H3 K9me3 peptide

Structural highlights

5fb1 is a 2 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 2.1Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SP100_HUMAN Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation.[1] [2] [3] [4] [5] [6] [7] [8] [9]

References

  1. ↑ Wasylyk C, Schlumberger SE, Criqui-Filipe P, Wasylyk B. Sp100 interacts with ETS-1 and stimulates its transcriptional activity. Mol Cell Biol. 2002 Apr;22(8):2687-702. PMID:11909962
  2. ↑ Moller A, Sirma H, Hofmann TG, Staege H, Gresko E, Ludi KS, Klimczak E, Droge W, Will H, Schmitz ML. Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression. Oncogene. 2003 Nov 27;22(54):8731-7. PMID:14647468 doi:http://dx.doi.org/10.1038/sj.onc.1207079
  3. ↑ Yordy JS, Li R, Sementchenko VI, Pei H, Muise-Helmericks RC, Watson DK. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene. 2004 Aug 26;23(39):6654-65. PMID:15247905 doi:http://dx.doi.org/10.1038/sj.onc.1207891
  4. ↑ Yordy JS, Moussa O, Pei H, Chaussabel D, Li R, Watson DK. SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene. 2005 Jan 27;24(5):916-31. PMID:15592518 doi:http://dx.doi.org/10.1038/sj.onc.1208245
  5. ↑ Jiang WQ, Zhong ZH, Henson JD, Neumann AA, Chang AC, Reddel RR. Suppression of alternative lengthening of telomeres by Sp100-mediated sequestration of the MRE11/RAD50/NBS1 complex. Mol Cell Biol. 2005 Apr;25(7):2708-21. PMID:15767676 doi:http://dx.doi.org/10.1128/MCB.25.7.2708-2721.2005
  6. ↑ Ling PD, Peng RS, Nakajima A, Yu JH, Tan J, Moses SM, Yang WH, Zhao B, Kieff E, Bloch KD, Bloch DB. Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100. EMBO J. 2005 Oct 19;24(20):3565-75. Epub 2005 Sep 22. PMID:16177824 doi:http://dx.doi.org/7600820
  7. ↑ 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
  8. ↑ Held-Feindt J, Hattermann K, Knerlich-Lukoschus F, Mehdorn HM, Mentlein R. SP100 reduces malignancy of human glioma cells. Int J Oncol. 2011 Apr;38(4):1023-30. doi: 10.3892/ijo.2011.927. Epub 2011 Jan 27. PMID:21274506 doi:http://dx.doi.org/10.3892/ijo.2011.927
  9. ↑ Kim YE, Lee JH, Kim ET, Shin HJ, Gu SY, Seol HS, Ling PD, Lee CH, Ahn JH. Human cytomegalovirus infection causes degradation of Sp100 proteins that suppress viral gene expression. J Virol. 2011 Nov;85(22):11928-37. doi: 10.1128/JVI.00758-11. Epub 2011 Aug 31. PMID:21880768 doi:http://dx.doi.org/10.1128/JVI.00758-11

5fb1, resolution 2.10Å

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