2vjf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:01, 9 May 2024) (edit) (undo)
 
(11 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:2vjf.png|left|200px]]
 
-
<!--
+
==Crystal Structure of the MDM2-MDMX RING Domain Heterodimer==
-
The line below this paragraph, containing "STRUCTURE_2vjf", creates the "Structure Box" on the page.
+
<StructureSection load='2vjf' size='340' side='right'caption='[[2vjf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[2vjf]] 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=2VJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VJF FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
{{STRUCTURE_2vjf| PDB=2vjf | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vjf OCA], [https://pdbe.org/2vjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vjf RCSB], [https://www.ebi.ac.uk/pdbsum/2vjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vjf ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vj/2vjf_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vjf ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
MDM2, a ubiquitin E3-ligase of the RING family, has a key role in regulating p53 abundance. During normal non-stress conditions p53 is targeted for degradation by MDM2. MDM2 can also target itself and MDMX for degradation. MDMX is closely related to MDM2 but the RING domain of MDMX does not possess intrinsic E3-ligase activity. Instead, MDMX regulates p53 abundance by modulating the levels and activity of MDM2. Dimerization, mediated by the conserved C-terminal RING domains of both MDM2 and MDMX, is critical to this activity. Here we report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b). In both MDM2 and MDMX residues C-terminal to the RING domain have a key role in dimer formation. In addition we show that these residues are part of an extended surface that is essential for ubiquitylation in trans. This study provides a molecular basis for understanding how heterodimer formation leads to stabilization of MDM2, yet degradation of p53, and suggests novel targets for therapeutic intervention.Cell Death and Differentiation (2008) 15, 841-848; doi:10.1038/sj.cdd.4402309; published online 25 January 2008.
-
===CRYSTAL STRUCTURE OF THE MDM2-MDMX RING DOMAIN HETERODIMER===
+
Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans.,Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL Cell Death Differ. 2008 May;15(5):841-8. Epub 2008 Jan 25. PMID:18219319<ref>PMID:18219319</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 2vjf" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_18219319}}, adds the Publication Abstract to the page
+
*[[MDM2 3D structures|MDM2 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 18219319 is the PubMed ID number.
+
*[[MDM4|MDM4]]
-
-->
+
== References ==
-
{{ABSTRACT_PUBMED_18219319}}
+
<references/>
-
 
+
__TOC__
-
==About this Structure==
+
</StructureSection>
-
2VJF is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJF OCA].
+
-
 
+
-
==Reference==
+
-
Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans., Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL, Cell Death Differ. 2008 May;15(5):841-8. Epub 2008 Jan 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18219319 18219319]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
-
[[Category: Day, C L.]]
+
[[Category: Day CL]]
-
[[Category: Linke, K.]]
+
[[Category: Linke K]]
-
[[Category: Mace, P D.]]
+
[[Category: Mace PD]]
-
[[Category: Smith, C A.]]
+
[[Category: Smith CA]]
-
[[Category: Alternative splicing]]
+
-
[[Category: Cytoplasm]]
+
-
[[Category: Host-virus interaction]]
+
-
[[Category: Ligase]]
+
-
[[Category: Mdm]]
+
-
[[Category: Metal-binding]]
+
-
[[Category: Nucleus]]
+
-
[[Category: Phosphorylation]]
+
-
[[Category: Polymorphism]]
+
-
[[Category: Proto-oncogene]]
+
-
[[Category: Ring]]
+
-
[[Category: Ubl conjugation pathway]]
+
-
[[Category: Zinc]]
+
-
[[Category: Zinc-finger]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:16:32 2008''
+

Current revision

Crystal Structure of the MDM2-MDMX RING Domain Heterodimer

PDB ID 2vjf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vjf"
Personal tools