View source for 2yhn


==The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor==
<StructureSection load='2yhn' size='340' side='right'caption='[[2yhn]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2yhn]] 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=2YHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YHN 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]] 3&#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=2yhn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yhn OCA], [https://pdbe.org/2yhn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yhn RCSB], [https://www.ebi.ac.uk/pdbsum/2yhn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yhn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MYLIP_HUMAN MYLIP_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.<ref>PMID:10593918</ref> <ref>PMID:14550572</ref> <ref>PMID:12826659</ref> <ref>PMID:19520913</ref> <ref>PMID:20427281</ref> <ref>PMID:22109552</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We previously identified the E3 ubiquitin ligase IDOL as a sterol-dependent regulator of the LDL receptor (LDLR). The molecular pathway underlying IDOL action, however, remains to be determined. Here we report the identification and biochemical and structural characterization of an E2-E3 ubiquitin ligase complex for LDLR degradation. We identified the UBE2D family (UBE2D1-4) as E2 partners for IDOL that support both autoubiquitination and IDOL-dependent ubiquitination of the LDLR in a cell-free system. NMR chemical shift mapping and a 2.1 A crystal structure of the IDOL RING domain-UBE2D1 complex revealed key interactions between the dimeric IDOL protein and the E2 enzyme. Analysis of the IDOL-UBE2D1 interface also defined the stereochemical basis for the selectivity of IDOL for UBE2Ds over other E2 ligases. Structure-based mutations that inhibit IDOL dimerization or IDOL-UBE2D interaction block IDOL-dependent LDLR ubiquitination and degradation. Furthermore, expression of a dominant-negative UBE2D enzyme inhibits the ability of IDOL to degrade the LDLR in cells. These results identify the IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake.

The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor.,Zhang L, Fairall L, Goult BT, Calkin AC, Hong C, Millard CJ, Tontonoz P, Schwabe JW Genes Dev. 2011 Jun 15;25(12):1262-74. PMID:21685362<ref>PMID:21685362</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2yhn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fairall L]]
[[Category: Goult BT]]
[[Category: Millard CJ]]
[[Category: Schwabe JWR]]
[[Category: Tontonoz P]]