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4mi8

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{{STRUCTURE_4mi8| PDB=4mi8 | SCENE= }}
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==Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and a Beclin 1 BH3 domain-derived peptide==
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===Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and a Beclin 1 BH3 domain-derived peptide===
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<StructureSection load='4mi8' size='340' side='right' caption='[[4mi8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4mi8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mhv68 Mhv68]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MI8 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dvu|3dvu]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAMMAHV.M11, M11, v-bcl-2, v-bcl-2 GAMMAHV.M11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33708 MHV68])</td></tr>
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<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=4mi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mi8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mi8 RCSB], [http://www.ebi.ac.uk/pdbsum/4mi8 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Function==
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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>
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[[http://www.uniprot.org/uniprot/BECN1_HUMAN BECN1_HUMAN]] Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense. Protects against infection by a neurovirulent strain of Sindbis virus.<ref>PMID:20208530</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4mi8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MI8 OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<references group="xtra"/><references/>
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__TOC__
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</StructureSection>
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[[Category: Mhv68]]
[[Category: Mei, Y.]]
[[Category: Mei, Y.]]
[[Category: Su, M.]]
[[Category: Su, M.]]

Revision as of 05:30, 8 October 2014

Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and a Beclin 1 BH3 domain-derived peptide

4mi8, resolution 2.10Å

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