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5fmj

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Revision as of 07:26, 6 May 2020

Bcl-xL with mouse Bak BH3 Q75L complex

Structural highlights

5fmj is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5fmi, 5fmk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.^[1] ^[2] Isoform Bcl-X(S) promotes apoptosis.^[3] ^[4]

Publication Abstract from PubMed

Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. Mechanistic insights have primarily been gleaned from in vitro studies because genetic approaches in mammals that produce unambiguous data are difficult to design. Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. In vitro, Bak(Q75L) cells were significantly more sensitive to various apoptotic stimuli. In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak.

Physiological restraint of Bak by Bcl-xL is essential for cell survival.,Lee EF, Grabow S, Chappaz S, Dewson G, Hockings C, Kluck RM, Debrincat MA, Gray DH, Witkowski MT, Evangelista M, Pettikiriarachchi A, Bouillet P, Lane RM, Czabotar PE, Colman PM, Smith BJ, Kile BT, Fairlie WD Genes Dev. 2016 May 15;30(10):1240-50. doi: 10.1101/gad.279414.116. Epub 2016 May, 19. PMID:27198225^[5]

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

References

↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Lee EF, Grabow S, Chappaz S, Dewson G, Hockings C, Kluck RM, Debrincat MA, Gray DH, Witkowski MT, Evangelista M, Pettikiriarachchi A, Bouillet P, Lane RM, Czabotar PE, Colman PM, Smith BJ, Kile BT, Fairlie WD. Physiological restraint of Bak by Bcl-xL is essential for cell survival. Genes Dev. 2016 May 15;30(10):1240-50. doi: 10.1101/gad.279414.116. Epub 2016 May, 19. PMID:27198225 doi:http://dx.doi.org/10.1101/gad.279414.116

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/5fmj"

@@ Line 1: / Line 1: @@
 ==Bcl-xL with mouse Bak BH3 Q75L complex==
-<StructureSection load='5fmj' size='340' side='right' caption='[[5fmj]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
+<StructureSection load='5fmj' size='340' side='right'caption='[[5fmj]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fmj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FMJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fmj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FMJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FMJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fmi|5fmi]], [[5fmk|5fmk]]</td></tr>
-<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=5fmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fmj OCA], [http://pdbe.org/5fmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fmj RCSB], [http://www.ebi.ac.uk/pdbsum/5fmj PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fmj OCA], [http://pdbe.org/5fmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fmj RCSB], [http://www.ebi.ac.uk/pdbsum/5fmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fmj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5fmj" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Fairlie, W D]]
 [[Category: Lee, E F]]

5fmj

From Proteopedia

Revision as of 07:26, 6 May 2020

Bcl-xL with mouse Bak BH3 Q75L complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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