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4b4s

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Revision as of 08:23, 5 August 2016

Crystal Structure of a pro-survival Bcl-2:Bim BH3 complex

Structural highlights

4b4s 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:	2v6q, 2vm6, 2wh6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2L10_HUMAN] Promotes cell survival. Suppresses apoptosis induced by BAX but not BAK.^[1] [B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

B-cell lymphoma-2 (Bcl-2) proteins mediate intrinsic-, or mitochondrial-, initiated apoptosis. We have investigated the structure and function of the least characterized Bcl-2 family member, Bcl-B, solving the crystal structure of a Bcl-B:Bim complex to 1.9 A resolution. Bcl-B is distinguished from other Bcl-2 family members through an insertion of an unstructured loop between helices alpha5 and alpha6. Probing Bcl-B interactions with Bcl-2 homology (BH)3 motifs using a combination of biophysical- and cell-based assays revealed a unique BH3-only protein binding profile. Bcl-B has high-affinity interactions with Bim and Bik only. Our results not only delineate the mode of action of Bcl-B but also complete our understanding of the specific interactions between BH3-only proteins and their prosurvival Bcl-2 counterparts. Notably, we conclude that Bim is the universal prosurvival antagonist as no other BH3-only protein binds all six prosurvival proteins and that Mcl-1 and Bcl-x(L) form a distinct prosurvival dyad.

The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist.,Rautureau GJ, Yabal M, Yang H, Huang DC, Kvansakul M, Hinds MG Cell Death Dis. 2012 Dec 13;3:e443. doi: 10.1038/cddis.2012.178. PMID:23235460^[8]

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

References

↑ Ke N, Godzik A, Reed JC. Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak. J Biol Chem. 2001 Apr 20;276(16):12481-4. Epub 2001 Feb 21. PMID:11278245 doi:http://dx.doi.org/10.1074/jbc.C000871200
↑ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95. PMID:9430630 doi:http://dx.doi.org/10.1093/emboj/17.2.384
↑ U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41. PMID:11734221
↑ Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002 May 15;62(10):2976-81. PMID:12019181
↑ Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002 Jun;22(11):3577-89. PMID:11997495
↑ Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM. Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61. PMID:15147734 doi:http://dx.doi.org/10.1016/j.biocel.2003.12.015
↑ Fukazawa H, Noguchi K, Masumi A, Murakami Y, Uehara Y. BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther. 2004 Oct;3(10):1281-8. PMID:15486195
↑ Rautureau GJ, Yabal M, Yang H, Huang DC, Kvansakul M, Hinds MG. The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist. Cell Death Dis. 2012 Dec 13;3:e443. doi: 10.1038/cddis.2012.178. PMID:23235460 doi:http://dx.doi.org/10.1038/cddis.2012.178

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b4s"

Categories: Human | Hinds, M G | Kvansakul, M | Rautureau, G J.P | Apoptosis

@@ Line 1: / Line 1: @@
 ==Crystal Structure of a pro-survival Bcl-2:Bim BH3 complex==
 <StructureSection load='4b4s' size='340' side='right' caption='[[4b4s]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B4S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b4s]] 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=4B4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B4S FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2v6q|2v6q]], [[2vm6|2vm6]], [[2wh6|2wh6]]</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=4b4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b4s RCSB], [http://www.ebi.ac.uk/pdbsum/4b4s PDBsum]</span></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=4b4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b4s OCA], [http://pdbe.org/4b4s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4b4s RCSB], [http://www.ebi.ac.uk/pdbsum/4b4s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4b4s ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
+[[http://www.uniprot.org/uniprot/B2L10_HUMAN B2L10_HUMAN]] Promotes cell survival. Suppresses apoptosis induced by BAX but not BAK.<ref>PMID:11278245</ref>  [[http://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4b4s" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Hinds, M G]]
 [[Category: Kvansakul, M]]
 [[Category: Rautureau, G J.P]]
 [[Category: Apoptosis]]

4b4s

From Proteopedia

Revision as of 08:23, 5 August 2016

Crystal Structure of a pro-survival Bcl-2:Bim BH3 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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