View source for 2lxh

==NMR structure of the RING domain in ubiquitin ligase gp78==
<StructureSection load='2lxh' size='340' side='right' caption='[[2lxh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2lxh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LXH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMFR, RNF45 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lxh OCA], [http://pdbe.org/2lxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lxh RCSB], [http://www.ebi.ac.uk/pdbsum/2lxh PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/AMFR_HUMAN AMFR_HUMAN]] E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor.<ref>PMID:10456327</ref> <ref>PMID:11724934</ref> <ref>PMID:16168377</ref> <ref>PMID:19103148</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RING finger proteins constitute the large majority of ubiquitin ligases (E3s) and function by interacting with ubiquitin-conjugating enzymes (E2s) charged with ubiquitin. How low-affinity RING-E2 interactions result in highly processive substrate ubiquitination is largely unknown. The RING E3, gp78, represents an excellent model to study this process. gp78 includes a high-affinity secondary binding region for its cognate E2, Ube2g2, the G2BR. The G2BR allosterically enhances RING:Ube2g2 binding and ubiquitination. Structural analysis of the RING:Ube2g2:G2BR complex reveals that a G2BR-induced conformational effect at the RING:Ube2g2 interface is necessary for enhanced binding of RING to Ube2g2 or Ube2g2 conjugated to Ub. This conformational effect and a key ternary interaction with conjugated ubiquitin are required for ubiquitin transfer. Moreover, RING:Ube2g2 binding induces a second allosteric effect, disrupting Ube2g2:G2BR contacts, decreasing affinity and facilitating E2 exchange. Thus, gp78 is a ubiquitination machine where multiple E2-binding sites coordinately facilitate processive ubiquitination.

Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine.,Das R, Liang YH, Mariano J, Li J, Huang T, King A, Tarasov SG, Weissman AM, Ji X, Byrd RA EMBO J. 2013 Aug 13. doi: 10.1038/emboj.2013.174. PMID:23942235<ref>PMID:23942235</ref>

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

==See Also==
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Byrd, R]]
[[Category: Das, R]]
[[Category: Huang, T]]
[[Category: Ji, X]]
[[Category: King, A]]
[[Category: Li, J]]
[[Category: Linag, Y]]
[[Category: Mariano, J]]
[[Category: Weissman, A]]
[[Category: Ligase]]
[[Category: Ring domain]]
[[Category: Ubiquitin]]