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[[Image:2ims.jpg|left|200px]]<br /><applet load="2ims" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2ims, resolution 1.48&Aring;" />
'''The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site'''<br />


==Overview==
==The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site==
BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP), drives cell death during development and tissue homeostasis from zebrafish, to humans. In most cancers, this pathway is inhibited by BCL-2 family, antiapoptotic members, which bind and block the action of proapoptotic BCL, proteins. We report the 1.5 A crystal structure of calpain-proteolysed, BAK, cBAK, to reveal a zinc binding site that regulates its activity via, homodimerization. cBAK contains an occluded BH3 peptide binding pocket, that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires, activation by truncated BID to induce cytochrome c release in mitochondria, isolated from bak/bax double-knockout mouse embryonic fibroblasts. The, BAK-mediated MOMP is inhibited by low micromolar zinc levels. This, inhibition is alleviated by mutation of the zinc-coordination site in BAK., Our results link directly the antiapoptotic effects of zinc to BAK.
<StructureSection load='2ims' size='340' side='right'caption='[[2ims]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ims]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMS 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]] 1.48&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2ims FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ims OCA], [https://pdbe.org/2ims PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ims RCSB], [https://www.ebi.ac.uk/pdbsum/2ims PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ims ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BAK_HUMAN BAK_HUMAN] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.<ref>PMID:8521816</ref> <ref>PMID:17157251</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2ims_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ims ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) drives cell death during development and tissue homeostasis from zebrafish to humans. In most cancers, this pathway is inhibited by BCL-2 family antiapoptotic members, which bind and block the action of proapoptotic BCL proteins. We report the 1.5 A crystal structure of calpain-proteolysed BAK, cBAK, to reveal a zinc binding site that regulates its activity via homodimerization. cBAK contains an occluded BH3 peptide binding pocket that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires activation by truncated BID to induce cytochrome c release in mitochondria isolated from bak/bax double-knockout mouse embryonic fibroblasts. The BAK-mediated MOMP is inhibited by low micromolar zinc levels. This inhibition is alleviated by mutation of the zinc-coordination site in BAK. Our results link directly the antiapoptotic effects of zinc to BAK.


==About this Structure==
The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site.,Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251<ref>PMID:17157251</ref>
2IMS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IMS OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site., Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K, Mol Cell. 2006 Dec 8;24(5):677-88. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17157251 17157251]
</div>
<div class="pdbe-citations 2ims" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Gehring, K.B.]]
[[Category: Gehring KB]]
[[Category: Liu, Q.]]
[[Category: Liu Q]]
[[Category: Moldoveanu, T.]]
[[Category: Moldoveanu T]]
[[Category: Shore, G.C.]]
[[Category: Shore GC]]
[[Category: Tocilj, A.]]
[[Category: Tocilj A]]
[[Category: Watson, M.]]
[[Category: Watson M]]
[[Category: ZN]]
[[Category: dimer]]
 
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Retrieved from "https://proteopedia.org/2ims"