View source for 5ezu


==Crystal structure of the N-terminal domain of vaccinia virus immunomodulator A46 in complex with myristic acid.==
<StructureSection load='5ezu' size='340' side='right'caption='[[5ezu]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ezu]] is a 2 chain structure with sequence from [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=5EZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EZU 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=5ezu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezu OCA], [https://pdbe.org/5ezu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ezu RCSB], [https://www.ebi.ac.uk/pdbsum/5ezu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A46_VACCW A46_VACCW] Bcl-2-like protein which disrupts the host immune response by inhibiting the TLR4 signaling pathway leading to NF-kappa-B activation. Targets several host TIR adapters including MYD88, TIRAP, TRIF and TICAM2 thereby blocking NF-kappa-B and TRIF-mediated IRF3 activation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins. We have previously determined the X-ray structure of the A46 C-terminal domain; however, the structure and function of the A46 N-terminal domain and its relationship to the C-terminal domain have remained unclear. Here, we biophysically characterize residues 1-83 of the N-terminal domain of A46 and present the X-ray structure at 1.55 A. Crystallographic phases were obtained by a recently developed ab initio method entitled ARCIMBOLDO_BORGES that employs tertiary structure libraries extracted from the Protein Data Bank; data analysis revealed an all beta-sheet structure. This is the first such structure solved by this method which should be applicable to any protein composed entirely of beta-sheets. The A46(1-83) structure itself is a beta-sandwich containing a co-purified molecule of myristic acid inside a hydrophobic pocket and represents a previously unknown lipid-binding fold. Mass spectrometry analysis confirmed the presence of long-chain fatty acids in both N-terminal and full-length A46; mutation of the hydrophobic pocket reduced the lipid content. Using a combination of high resolution X-ray structures of the N- and C-terminal domains and SAXS analysis of full-length protein A46(1-240), we present here a structural model of A46 in a tetrameric assembly. Integrating affinity measurements and structural data, we propose how A46 simultaneously interferes with several TIR-domain containing proteins to inhibit NF-kappaB activation and postulate that A46 employs a bipartite binding arrangement to sequester the host immune adaptors TRAM and MyD88.

Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins.,Fedosyuk S, Bezerra GA, Radakovics K, Smith TK, Sammito M, Bobik N, Round A, Ten Eyck LF, Djinovic-Carugo K, Uson I, Skern T PLoS Pathog. 2016 Dec 14;12(12):e1006079. doi: 10.1371/journal.ppat.1006079., eCollection 2016 Dec. PMID:27973613<ref>PMID:27973613</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 5ezu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Vaccinia virus WR]]
[[Category: Bezerra GA]]
[[Category: Fedosyuk S]]
[[Category: Sammito M]]
[[Category: Skern T]]
[[Category: Uson I]]