View source for 6i2m


==Crystal structure of vaccinia virus protein A55 BTB-Back domain in complex with human Cullin-3 N-terminus==
<StructureSection load='6i2m' size='340' side='right'caption='[[6i2m]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6i2m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vaccinia_virus_WR Vaccinia virus WR]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I2M 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]] 2.3&#8491;</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=6i2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2m OCA], [https://pdbe.org/6i2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i2m RCSB], [https://www.ebi.ac.uk/pdbsum/6i2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2m ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KBTB1_VACCW KBTB1_VACCW] Probable substrate-specific adapter of CUL3-containing E3 ubiquitin-protein ligases which mediate the ubiquitination and subsequent proteasomal degradation of host target proteins.
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== Publication Abstract from PubMed ==
BTB-Kelch proteins are substrate-specific adaptors for cullin-3 (Cul3) RING-box-based E3 ubiquitin ligases, mediating protein ubiquitylation for subsequent proteasomal degradation. Vaccinia virus encodes three BTB-Kelch proteins: A55, C2, and F3. Viruses lacking A55 or C2 have altered cytopathic effects in cultured cells and altered pathology in vivo Previous studies have shown that the ectromelia virus orthologue of A55 interacts with Cul3 in cells. We report that the N-terminal BTB-BACK (BB) domain of A55 binds directly to the Cul3 N-terminal domain (Cul3-NTD), forming a 2:2 complex in solution. We solved the structure of an A55BB/Cul3-NTD complex from anisotropic crystals diffracting to 2.3/3.7 A resolution in the best/worst direction, revealing that the overall interaction and binding interface closely resembles the structures of cellular BTB/Cul3-NTD complexes, despite low sequence identity between A55 and cellular BTB domains. Surprisingly, despite this structural similarity, the affinity of Cul3-NTD for A55BB was stronger than for cellular BTB proteins. Glutamate substitution of A55 residue Ile 48, adjacent to the canonical varphi-X-D/E Cul3-binding motif, reduced affinity of A55BB for Cul3-NTD by at least two orders of magnitude. Moreover, Ile 48 and the varphi-X-D/E motif are conserved in A55 orthologs from other poxviruses, but not in the vaccinia virus proteins C2 or F3. The high-affinity interaction between A55BB and Cul3-NTD suggests that, in addition to directing the Cul3-RING E3 ligase complex to degrade cellular/viral target proteins that are normally unaffected, A55 may also sequester Cul3 from cellular adaptor proteins, thereby protecting substrates of these cellular adaptors from ubiquitylation and degradation.

Molecular basis of cullin-3 (Cul3) ubiquitin ligase subversion by vaccinia virus protein A55.,Gao C, Pallett MA, Croll TI, Smith GL, Graham SC J Biol Chem. 2019 Feb 28. pii: RA118.006561. doi: 10.1074/jbc.RA118.006561. PMID:30819806<ref>PMID:30819806</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6i2m" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cullin 3D structures|Cullin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Vaccinia virus WR]]
[[Category: Gao G]]
[[Category: Graham SC]]