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2k7w

From Proteopedia

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BAX Activation is Initiated at a Novel Interaction Site

Structural highlights

2k7w is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BAX_HUMAN Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.

BAX activation is initiated at a novel interaction site.,Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD Nature. 2008 Oct 23;455(7216):1076-81. PMID:18948948^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609-19. PMID:8358790
↑ Schmitt E, Paquet C, Beauchemin M, Dever-Bertrand J, Bertrand R. Characterization of Bax-sigma, a cell death-inducing isoform of Bax. Biochem Biophys Res Commun. 2000 Apr 21;270(3):868-79. PMID:10772918 doi:http://dx.doi.org/10.1006/bbrc.2000.2537
↑ 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
↑ Zhang H, Kim JK, Edwards CA, Xu Z, Taichman R, Wang CY. Clusterin inhibits apoptosis by interacting with activated Bax. Nat Cell Biol. 2005 Sep;7(9):909-15. Epub 2005 Aug 21. PMID:16113678 doi:http://dx.doi.org/10.1038/ncb1291
↑ Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site. Nature. 2008 Oct 23;455(7216):1076-81. PMID:18948948 doi:10.1038/nature07396
↑ Czabotar PE, Lee EF, Thompson GV, Wardak AZ, Fairlie WD, Colman PM. Mutation to Bax beyond the BH3 domain disrupts interactions with pro-survival proteins and promotes apoptosis. J Biol Chem. 2011 Mar 4;286(9):7123-31. Epub 2011 Jan 3. PMID:21199865 doi:10.1074/jbc.M110.161281
↑ Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site. Nature. 2008 Oct 23;455(7216):1076-81. PMID:18948948 doi:10.1038/nature07396

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2k7w"

@@ Line 1: / Line 1: @@
 ==BAX Activation is Initiated at a Novel Interaction Site==
-<StructureSection load='2k7w' size='340' side='right' caption='[[2k7w]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2k7w' size='340' side='right'caption='[[2k7w]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2k7w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K7W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K7W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2k7w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K7W FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f16|1f16]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2k7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k7w OCA], [https://pdbe.org/2k7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k7w RCSB], [https://www.ebi.ac.uk/pdbsum/2k7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k7w ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k7w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k7w RCSB], [http://www.ebi.ac.uk/pdbsum/2k7w PDBsum]</span></td></tr>
+</table>
-<table>
+== Function ==
+[https://www.uniprot.org/uniprot/BAX_HUMAN BAX_HUMAN] Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.<ref>PMID:8358790</ref> <ref>PMID:10772918</ref> <ref>PMID:8521816</ref> <ref>PMID:16113678</ref> <ref>PMID:18948948</ref> <ref>PMID:21199865</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/k7/2k7w_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k7/2k7w_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2k7w ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2k7w" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
@@ Line 30: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bird, G H.]]
+[[Category: Large Structures]]
-[[Category: Cheng, E H.]]
+[[Category: Bird GH]]
-[[Category: Davis, M L.]]
+[[Category: Cheng EH]]
-[[Category: Gavathiotis, E.]]
+[[Category: Davis ML]]
-[[Category: Katz, S G.]]
+[[Category: Gavathiotis E]]
-[[Category: Kim, H.]]
+[[Category: Katz SG]]
-[[Category: Pitter, K.]]
+[[Category: Kim H]]
-[[Category: Suzuki, M.]]
+[[Category: Pitter K]]
-[[Category: Tjandra, N.]]
+[[Category: Suzuki M]]
-[[Category: Tu, H C.]]
+[[Category: Tjandra N]]
-[[Category: Walensky, L D.]]
+[[Category: Tu HC]]
-[[Category: Apoptosis]]
+[[Category: Walensky LD]]
-[[Category: Bax]]
-[[Category: Bcl-2]]
-[[Category: Bh3]]
-[[Category: Bim]]

2k7w

From Proteopedia

Current revision

BAX Activation is Initiated at a Novel Interaction Site

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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