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| | ==The NMR structure of the BID-BAK complex== | | ==The NMR structure of the BID-BAK complex== |
| - | <StructureSection load='2m5b' size='340' side='right'caption='[[2m5b]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m5b' size='340' side='right'caption='[[2m5b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m5b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M5B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m5b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M5B FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2imt|2imt]], [[2bid|2bid]]</div></td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAK, BAK1, BCL2L7, CDN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m5b OCA], [https://pdbe.org/2m5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m5b RCSB], [https://www.ebi.ac.uk/pdbsum/2m5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m5b ProSAT]</span></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=2m5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m5b OCA], [https://pdbe.org/2m5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m5b RCSB], [https://www.ebi.ac.uk/pdbsum/2m5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m5b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Grace, C R]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Green, D R]] | + | [[Category: Grace CR]] |
| - | [[Category: Kriwacki, R W]] | + | [[Category: Green DR]] |
| - | [[Category: Moldoveanu, T]] | + | [[Category: Kriwacki RW]] |
| - | [[Category: Apoptosis]] | + | [[Category: Moldoveanu T]] |
| - | [[Category: Bcl-2 family effector bak]]
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| - | [[Category: Bh3-only protein bid]]
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| - | [[Category: Effector direct activation]]
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| - | [[Category: Mitochondrial outer membrane premeabilization]]
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| - | [[Category: Nmr solution structure of bid-bak complex]]
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| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis. The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function. We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK. Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID. BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization. BAK activation follows a 'hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface. In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK. These findings provide insights into the early stages of BAK activation.
BID-induced structural changes in BAK promote apoptosis.,Moldoveanu T, Grace CR, Llambi F, Nourse A, Fitzgerald P, Gehring K, Kriwacki RW, Green DR Nat Struct Mol Biol. 2013 May;20(5):589-97. doi: 10.1038/nsmb.2563. Epub 2013 Apr, 21. PMID:23604079[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995 Nov 15;14(22):5589-96. PMID:8521816
- ↑ Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
- ↑ Moldoveanu T, Grace CR, Llambi F, Nourse A, Fitzgerald P, Gehring K, Kriwacki RW, Green DR. BID-induced structural changes in BAK promote apoptosis. Nat Struct Mol Biol. 2013 May;20(5):589-97. doi: 10.1038/nsmb.2563. Epub 2013 Apr, 21. PMID:23604079 doi:10.1038/nsmb.2563
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