7k02: Difference between revisions

Latest revision as of 15:15, 18 October 2023

The crystal structure of a BAK dimer activated by detergent

Structural highlights

7k02 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BAK_HUMAN In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.^[1] ^[2]

Publication Abstract from PubMed

A body of data supports the existence of core (alpha2-alpha5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK alpha2-alpha8 dimers (i.e., minus its flexible N-terminal helix and membrane-anchoring C-terminal segment) that has been obtained through the activation of monomeric BAK with the detergent C12E8. Core dimers are evident, linked through the crystal by contacts via latch (alpha6-alpha8) domains. This crystal structure shows activated BAK dimers with the extended latch domain present. Our data provide direct evidence for the conformational change converting BAK from inert monomer to the functional dimer that destroys mitochondrial integrity. This dimer is the smallest functional unit for recombinant BAK or BAX described so far.

Structure of detergent-activated BAK dimers derived from the inert monomer.,Birkinshaw RW, Iyer S, Lio D, Luo CS, Brouwer JM, Miller MS, Robin AY, Uren RT, Dewson G, Kluck RM, Colman PM, Czabotar PE Mol Cell. 2021 Mar 23. pii: S1097-2765(21)00182-9. doi:, 10.1016/j.molcel.2021.03.014. PMID:33794146^[3]

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

References

↑ 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
↑ Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
↑ Birkinshaw RW, Iyer S, Lio D, Luo CS, Brouwer JM, Miller MS, Robin AY, Uren RT, Dewson G, Kluck RM, Colman PM, Czabotar PE. Structure of detergent-activated BAK dimers derived from the inert monomer. Mol Cell. 2021 Mar 23. pii: S1097-2765(21)00182-9. doi:, 10.1016/j.molcel.2021.03.014. PMID:33794146 doi:https://dx.doi.org/10.1016/j.molcel.2021.03.014

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014

[3] Birkinshaw RW, Iyer S, Lio D, Luo CS, Brouwer JM, Miller MS, Robin AY, Uren RT, Dewson G, Kluck RM, Colman PM, Czabotar PE. Structure of detergent-activated BAK dimers derived from the inert monomer. Mol Cell. 2021 Mar 23. pii: S1097-2765(21)00182-9. doi:, 10.1016/j.molcel.2021.03.014. PMID:33794146 doi:https://dx.doi.org/10.1016/j.molcel.2021.03.014

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='7k02' size='340' side='right'caption='[[7k02]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7k02]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K02 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7k02]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K02 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4u2v|4u2v]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAK1, BAK, BCL2L7, CDN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7k02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k02 OCA], [https://pdbe.org/7k02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k02 RCSB], [https://www.ebi.ac.uk/pdbsum/7k02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k02 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/BAK_HUMAN BAK_HUMAN]] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.<ref>PMID:8521816</ref> <ref>PMID:17157251</ref>
+[https://www.uniprot.org/uniprot/BAK_HUMAN BAK_HUMAN] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.<ref>PMID:8521816</ref> <ref>PMID:17157251</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 18: @@
 </div>
 <div class="pdbe-citations 7k02" 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: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Birkinshaw, R W]]
+[[Category: Birkinshaw RW]]
-[[Category: Czabotar, P E]]
+[[Category: Czabotar PE]]
-[[Category: Apoptosis]]
-[[Category: Bak]]
-[[Category: Bcl-2 fold]]
-[[Category: Bh3-in-groove dimer]]
-[[Category: Pore forming]]
-[[Category: Proapoptotic]]

7k02: Difference between revisions

Latest revision as of 15:15, 18 October 2023

The crystal structure of a BAK dimer activated by detergent

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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