View source for 5yuf


==Crystal Structure of PML RING tetramer==
<StructureSection load='5yuf' size='340' side='right'caption='[[5yuf]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yuf]] is a 4 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=5YUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YUF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yuf OCA], [https://pdbe.org/5yuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yuf RCSB], [https://www.ebi.ac.uk/pdbsum/5yuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yuf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PML_HUMAN PML_HUMAN] Note=A chromosomal aberration involving PML may be a cause of acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) with RARA. The PML breakpoints (type A and type B) lie on either side of an alternatively spliced exon.<ref>PMID:1652369</ref> <ref>PMID:1720570</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PML_HUMAN PML_HUMAN] Key component of PML nuclear bodies that regulate a large number of cellular processes by facilitating post-translational modification of target proteins, promoting protein-protein contacts, or by sequestering proteins. Functions as tumor suppressor. Required for normal, caspase-dependent apoptosis in response to DNA damage, FAS, TNF, or interferons. Plays a role in transcription regulation, DNA damage response, DNA repair and chromatin organization. Plays a role in processes regulated by retinoic acid, regulation of cell division, terminal differentiation of myeloid precursor cells and differentiation of neural progenitor cells. Required for normal immunity to microbial infections. Plays a role in antiviral response. In the cytoplasm, plays a role in TGFB1-dependent processes. Regulates p53/TP53 levels by inhibiting its ubiquitination and proteasomal degradation. Regulates activation of p53/TP53 via phosphorylation at 'Ser-20'. Sequesters MDM2 in the nucleolus after DNA damage, and thereby inhibits ubiquitination and degradation of p53/TP53. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates RB1 phosphorylation and activity. Required for normal development of the brain cortex during embryogenesis. Can sequester herpes virus and varicella virus proteins inside PML bodies, and thereby inhibit the formation of infectious viral particles. Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum (By similarity). Regulates transcription activity of ELF4. Inhibits specifically the activity of the tetrameric form of PKM. Together with SATB1, involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Regulates PTEN compartmentalization through the inhibition of USP7-mediated deubiquitination.<ref>PMID:9756909</ref> <ref>PMID:10610177</ref> <ref>PMID:10684855</ref> <ref>PMID:11025664</ref> <ref>PMID:11432836</ref> <ref>PMID:12402044</ref> <ref>PMID:12439746</ref> <ref>PMID:12810724</ref> <ref>PMID:14976184</ref> <ref>PMID:15195100</ref> <ref>PMID:15356634</ref> <ref>PMID:17030982</ref> <ref>PMID:18298799</ref> <ref>PMID:18716620</ref> <ref>PMID:17173041</ref> <ref>PMID:19567472</ref> <ref>PMID:21172801</ref> <ref>PMID:21304940</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray crystallography and SAXS characterization, we demonstrate that PML RING tetramerizes through highly conserved PML-specific sequences, which are required for NB assembly and PML sumoylation. Conserved residues implicated in RING dimerization of other TRIMs also contribute to PML tetramer stability. Wild-type PML rescues the ability of some RING mutants to form NBs as well as their sumoylation. Impaired RING tetramerization abolishes PML/RARA-driven leukemogenesis in vivo and arsenic-induced differentiation ex vivo. Our studies thus identify RING tetramerization as a key step in the NB macro-molecular scaffolding. They suggest that higher order RING interactions allow efficient UBC9 recruitment and thus change the biochemical nature of TRIM-facilitated post-translational modifications.

RING tetramerization is required for nuclear body biogenesis and PML sumoylation.,Wang P, Benhenda S, Wu H, Lallemand-Breitenbach V, Zhen T, Jollivet F, Peres L, Li Y, Chen SJ, Chen Z, de The H, Meng G Nat Commun. 2018 Mar 29;9(1):1277. doi: 10.1038/s41467-018-03498-0. PMID:29599493<ref>PMID:29599493</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5yuf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Benhend S]]
[[Category: Breitenbach V]]
[[Category: Chen S]]
[[Category: Chen Z]]
[[Category: Jollivet F]]
[[Category: Li Y]]
[[Category: Meng G]]
[[Category: Peres L]]
[[Category: Wang P]]
[[Category: Wu H]]
[[Category: Zhen T]]
[[Category: De THE H]]