View source for 4mi8


==Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and a Beclin 1 BH3 domain-derived peptide==
<StructureSection load='4mi8' size='340' side='right'caption='[[4mi8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mi8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Murid_gammaherpesvirus_4 Murid gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MI8 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4mi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi8 OCA], [https://pdbe.org/4mi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mi8 RCSB], [https://www.ebi.ac.uk/pdbsum/4mi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mi8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ARBH_MHV68 ARBH_MHV68] Plays a role in the protection against apoptosis mediated by cytotoxic cells during the immune response to acute and persistent viral infection. Contributes therefore to latency establishment. Plays also a role in the inhibition of host starvation-induced autophagy which ultimately contributes to the viral chronic infection.<ref>PMID:10573168</ref> <ref>PMID:11205127</ref> <ref>PMID:15604429</ref> <ref>PMID:18248095</ref> <ref>PMID:18797192</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
gamma-herpesviruses (gammaHVs) are common human pathogens that encode homologs of the anti-apoptotic cellular Bcl-2 proteins, which are critical to viral reactivation and oncogenic transformation. The murine gammaHV68 provides a tractable in vivo model for understanding general features of these important human pathogens. Bcl-XL, a cellular Bcl-2 homolog, and the murine gammaHV68 Bcl-2 homolog, M11, both bind to a BH3 domain within the key autophagy effector Beclin 1 with comparable affinities, resulting in the down-regulation of Beclin 1-mediated autophagy. Despite this similarity, differences in residues lining the binding site of M11 and Bcl-XL dictate varying affinities for the different BH3 domain-containing proteins. Here we delineate Beclin 1 differential specificity determinants for binding to M11 or Bcl-XL by quantifying autophagy levels in cells expressing different Beclin 1 mutants and either M11 or Bcl-XL, and we show that a G120E/D121A Beclin 1 mutant selectively prevents down-regulation of Beclin 1-mediated autophagy by Bcl-XL, but not by M11. We use isothermal titration calorimetry to identify a Beclin 1 BH3 domain-derived peptide that selectively binds to M11, but not to Bcl-XL. The x-ray crystal structure of this peptide bound to M11 reveals the mechanism by which the M11 BH3 domain-binding groove accommodates this M11-specific peptide. This information was used to develop a cell-permeable peptide inhibitor that selectively inhibits M11-mediated, but not Bcl-XL-mediated, down-regulation of autophagy.

Targeting gamma-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.,Su M, Mei Y, Sanishvili R, Levine B, Colbert CL, Sinha S J Biol Chem. 2014 Mar 21;289(12):8029-40. doi: 10.1074/jbc.M113.515361. Epub 2014, Jan 17. PMID:24443581<ref>PMID:24443581</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4mi8" style="background-color:#fffaf0;"></div>

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Murid gammaherpesvirus 4]]
[[Category: Mei Y]]
[[Category: Sinha S]]
[[Category: Su M]]