2bzw

From Proteopedia

(Difference between revisions)

Revision as of 11:31, 30 March 2022

The crystal structure of BCL-XL in complex with full-length BAD

Structural highlights

2bzw is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1pq0, 1pq1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2CL1_MOUSE] 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] Isoform Bcl-X(S) promotes apoptosis (By similarity).^[2] [BAD_MOUSE] Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.

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

All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus.

Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine gamma-Herpesvirus 68.,Ku B, Woo JS, Liang C, Lee KH, Hong HS, E X, Kim KS, Jung JU, Oh BH PLoS Pathog. 2008 Feb 1;4(2):e25. PMID:18248095^[3]

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

References

↑ Yang XF, Weber GF, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity. 1997 Nov;7(5):629-39. PMID:9390687
↑ Yang XF, Weber GF, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity. 1997 Nov;7(5):629-39. PMID:9390687
↑ Ku B, Woo JS, Liang C, Lee KH, Hong HS, E X, Kim KS, Jung JU, Oh BH. Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine gamma-Herpesvirus 68. PLoS Pathog. 2008 Feb 1;4(2):e25. PMID:18248095 doi:07-PLPA-RA-0558

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/2bzw"

@@ Line 3: / Line 3: @@
 <StructureSection load='2bzw' size='340' side='right'caption='[[2bzw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2bzw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2BZW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2bzw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZW FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pq0|1pq0]], [[1pq1|1pq1]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pq0|1pq0]], [[1pq1|1pq1]]</div></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=2bzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bzw OCA], [http://pdbe.org/2bzw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bzw RCSB], [http://www.ebi.ac.uk/pdbsum/2bzw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bzw 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=2bzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bzw OCA], [https://pdbe.org/2bzw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bzw RCSB], [https://www.ebi.ac.uk/pdbsum/2bzw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bzw ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/B2CL1_MOUSE B2CL1_MOUSE]] 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.<ref>PMID:9390687</ref>   Isoform Bcl-X(S) promotes apoptosis (By similarity).<ref>PMID:9390687</ref>  [[http://www.uniprot.org/uniprot/BAD_MOUSE BAD_MOUSE]] Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.
+[[https://www.uniprot.org/uniprot/B2CL1_MOUSE B2CL1_MOUSE]] 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.<ref>PMID:9390687</ref>   Isoform Bcl-X(S) promotes apoptosis (By similarity).<ref>PMID:9390687</ref>  [[https://www.uniprot.org/uniprot/BAD_MOUSE BAD_MOUSE]] Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2bzw

From Proteopedia

Revision as of 11:31, 30 March 2022

The crystal structure of BCL-XL in complex with full-length BAD

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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