6l8v

From Proteopedia

(Difference between revisions)

Current revision

membrane-bound Bax helix2-helix5 domain

Structural highlights

6l8v 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.
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]

Publication Abstract from PubMed

Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high-resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both types of protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.

An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial membrane.,Lv F, Qi F, Zhang Z, Wen M, Kale J, Piai A, Du L, Wang S, Zhou L, Yang Y, Wu B, Liu Z, Del Rosario J, Pogmore J, Chou JJ, Andrews DW, Lin J, OuYang B EMBO J. 2021 Jul 15;40(14):e106438. doi: 10.15252/embj.2020106438. Epub 2021 Jun , 8. PMID:34101209^[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
↑ Lv F, Qi F, Zhang Z, Wen M, Kale J, Piai A, Du L, Wang S, Zhou L, Yang Y, Wu B, Liu Z, Del Rosario J, Pogmore J, Chou JJ, Andrews DW, Lin J, OuYang B. An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial membrane. EMBO J. 2021 Jul 15;40(14):e106438. doi: 10.15252/embj.2020106438. Epub 2021 Jun , 8. PMID:34101209 doi:http://dx.doi.org/10.15252/embj.2020106438

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6l8v"

Categories: Homo sapiens | Large Structures | Lv F | OuYang B

@@ Line 1: / Line 1: @@
 ==membrane-bound Bax helix2-helix5 domain==
-<StructureSection load='6l8v' size='340' side='right'caption='[[6l8v]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='6l8v' size='340' side='right'caption='[[6l8v]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6l8v]] 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=6L8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L8V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6l8v]] 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=6L8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L8V FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAX, BCL2L4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=6l8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8v OCA], [https://pdbe.org/6l8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l8v RCSB], [https://www.ebi.ac.uk/pdbsum/6l8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8v 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=6l8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8v OCA], [https://pdbe.org/6l8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l8v RCSB], [https://www.ebi.ac.uk/pdbsum/6l8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8v ProSAT]</span></td></tr>
 </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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lv, F]]
+[[Category: Lv F]]
-[[Category: OuYang, B]]
+[[Category: OuYang B]]
-[[Category: Apoptosis]]
-[[Category: Bax]]
-[[Category: Core-domain]]
-[[Category: Dimer]]
-[[Category: Membrane-bound]]
-[[Category: Stability]]

6l8v

From Proteopedia

Current revision

membrane-bound Bax helix2-helix5 domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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