4u2u: Difference between revisions

Latest revision as of 07:24, 27 September 2023

Bak domain swapped dimer induced by BidBH3 with CHAPS

Structural highlights

4u2u is a 2 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 2.9Å
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

Apoptotic stimuli activate and oligomerize the proapoptotic proteins Bak and Bax, resulting in mitochondrial outer-membrane permeabilization and subsequent cell death. This activation can occur when certain BH3-only proteins interact directly with Bak and Bax. Recently published crystal structures reveal that Bax separates into core and latch domains in response to BH3 peptides. The distinguishing characteristics of BH3 peptides capable of directly activating Bax were also elucidated. Here we identify specific BH3 peptides capable of "unlatching" Bak and describe structural insights into Bak activation and oligomerization. Crystal structures and crosslinking experiments demonstrate that Bak undergoes a conformational change similar to that of Bax upon activation. A structure of the Bak core domain dimer provides a high-resolution image of this key intermediate in the pore-forming oligomer. Our results confirm an analogous mechanism for activation and dimerization of Bak and Bax in response to certain BH3 peptides.

Bak Core and Latch Domains Separate during Activation, and Freed Core Domains Form Symmetric Homodimers.,Brouwer JM, Westphal D, Dewson G, Robin AY, Uren RT, Bartolo R, Thompson GV, Colman PM, Kluck RM, Czabotar PE Mol Cell. 2014 Aug 27. pii: S1097-2765(14)00609-1. doi:, 10.1016/j.molcel.2014.07.016. PMID:25175025^[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
↑ Brouwer JM, Westphal D, Dewson G, Robin AY, Uren RT, Bartolo R, Thompson GV, Colman PM, Kluck RM, Czabotar PE. Bak Core and Latch Domains Separate during Activation, and Freed Core Domains Form Symmetric Homodimers. Mol Cell. 2014 Aug 27. pii: S1097-2765(14)00609-1. doi:, 10.1016/j.molcel.2014.07.016. PMID:25175025 doi:https://dx.doi.org/10.1016/j.molcel.2014.07.016

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] Brouwer JM, Westphal D, Dewson G, Robin AY, Uren RT, Bartolo R, Thompson GV, Colman PM, Kluck RM, Czabotar PE. Bak Core and Latch Domains Separate during Activation, and Freed Core Domains Form Symmetric Homodimers. Mol Cell. 2014 Aug 27. pii: S1097-2765(14)00609-1. doi:, 10.1016/j.molcel.2014.07.016. PMID:25175025 doi:https://dx.doi.org/10.1016/j.molcel.2014.07.016

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[4u2u]] is a 2 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=4U2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U2U FirstGlance]. <br>
-</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=4u2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2u OCA], [https://pdbe.org/4u2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u2u RCSB], [https://www.ebi.ac.uk/pdbsum/4u2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u2u ProSAT]</span></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]] 2.9&#8491;</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=4u2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2u OCA], [https://pdbe.org/4u2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u2u RCSB], [https://www.ebi.ac.uk/pdbsum/4u2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u2u ProSAT]</span></td></tr>
 </table>
 == Function ==

4u2u: Difference between revisions

Latest revision as of 07:24, 27 September 2023

Bak domain swapped dimer induced by BidBH3 with CHAPS

Structural highlights

Function

Publication Abstract from PubMed

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References

Contents

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