This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2xa0

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 15:08, 8 July 2020

Crystal structure of BCL-2 in complex with a BAX BH3 peptide

Structural highlights

2xa0 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1ysw, 2w3l, 1g5m, 1gjh
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

Function

[BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).^[1] [BAX_MOUSE] 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. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production.^[2] ^[3]

Publication Abstract from PubMed

Interactions between the BCL-2 family proteins determine the cell's fate to live or die. How they interact with each other to regulate apoptosis remains as an unsettled central issue. So far, the antiapoptotic BCL-2 proteins are thought to interact with BAX weakly, but the physiological significance of this interaction has been vague. Herein, we show that recombinant BCL-2 and BCL-w interact potently with a BCL-2 homology (BH) 3 domain-containing peptide derived from BAX, exhibiting the dissociation constants of 15 and 23 nM, respectively. To clarify the basis for this strong interaction, we determined the three-dimensional structure of a complex of BCL-2 with a BAX peptide spanning its BH3 domain. It revealed that their interactions extended beyond the canonical BH3 domain and involved three nonconserved charged residues of BAX. A novel BAX variant, containing the alanine substitution of these three residues, had greatly impaired affinity for BCL-2 and BCL-w, but was otherwise indistinguishable from wild-type BAX. Critically, the apoptotic activity of the BAX variant could not be restrained by BCL-2 and BCL-w, pointing that the observed tight interactions are critical for regulating BAX activation. We also comprehensively quantified the binding affinities between the three BCL-2 subfamily proteins. Collectively, the data show that due to the high affinity of BAX for BCL-2, BCL-w and A1, and of BAK for BCL-X(L), MCL-1 and A1, only a subset of BH3-only proteins, commonly including BIM, BID and PUMA, could be expected to free BAX or BAK from the antiapoptotic BCL-2 proteins to elicit apoptosis.Cell Research advance online publication 9 November 2010; doi:10.1038/cr.2010.149.

Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX.,Ku B, Liang C, Jung JU, Oh BH Cell Res. 2010 Nov 9. PMID:21060336^[4]

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

References

↑ Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008 Jun 20;30(6):678-88. doi: 10.1016/j.molcel.2008.06.001. PMID:18570871 doi:10.1016/j.molcel.2008.06.001
↑ 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
↑ Ku B, Liang C, Jung JU, Oh BH. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res. 2010 Nov 9. PMID:21060336 doi:10.1038/cr.2010.149
↑ Ku B, Liang C, Jung JU, Oh BH. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res. 2010 Nov 9. PMID:21060336 doi:10.1038/cr.2010.149

1 Structural highlights
2 Disease
3 Function
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/2xa0"

@@ Line 1: / Line 1: @@
 ==Crystal structure of BCL-2 in complex with a BAX BH3 peptide==
-<StructureSection load='2xa0' size='340' side='right' caption='[[2xa0]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='2xa0' size='340' side='right'caption='[[2xa0]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xa0]] is a 4 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=2XA0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XA0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xa0]] is a 4 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=2XA0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XA0 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ysw|1ysw]], [[2w3l|2w3l]], [[1g5m|1g5m]], [[1gjh|1gjh]]</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=2xa0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa0 OCA], [http://pdbe.org/2xa0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xa0 RCSB], [http://www.ebi.ac.uk/pdbsum/2xa0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa0 ProSAT]</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=2xa0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa0 OCA], [http://pdbe.org/2xa0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xa0 RCSB], [http://www.ebi.ac.uk/pdbsum/2xa0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[B-cell lymphoma protein|B-cell lymphoma protein]]
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ku, B]]
 [[Category: Oh, B H]]
 [[Category: Apoptosis]]
 [[Category: Cell death]]

2xa0

From Proteopedia

Revision as of 15:08, 8 July 2020

Crystal structure of BCL-2 in complex with a BAX BH3 peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox