8igc

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Bak bound to Bnip5 BH3

Structural highlights

8igc 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 1.697Å
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

The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro-apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak-activating pro-apoptotic factor peroxisomal testis-enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak-mediated apoptosis.

Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain-containing protein.,Lim D, Jeong DE, Shin HC, Choi JS, Seo J, Kim SJ, Ku B Proteins. 2023 Aug 8. doi: 10.1002/prot.26568. PMID:37553948^[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
↑ Lim D, Jeong DE, Shin HC, Choi JS, Seo J, Kim SJ, Ku B. Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain-containing protein. Proteins. 2023 Aug 8. PMID:37553948 doi:10.1002/prot.26568

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/8igc"

Categories: Homo sapiens | Large Structures | Ku B | Lim D

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8igc is ON HOLD
+==Crystal structure of Bak bound to Bnip5 BH3==
+<StructureSection load='8igc' size='340' side='right'caption='[[8igc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8igc]] 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=8IGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IGC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.697&#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=8igc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8igc OCA], [https://pdbe.org/8igc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8igc RCSB], [https://www.ebi.ac.uk/pdbsum/8igc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8igc 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro-apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak-activating pro-apoptotic factor peroxisomal testis-enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak-mediated apoptosis.
-Authors:
+Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain-containing protein.,Lim D, Jeong DE, Shin HC, Choi JS, Seo J, Kim SJ, Ku B Proteins. 2023 Aug 8. doi: 10.1002/prot.26568. PMID:37553948<ref>PMID:37553948</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8igc" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ku B]]
+[[Category: Lim D]]

8igc

From Proteopedia

Current revision

Crystal structure of Bak bound to Bnip5 BH3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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