8ivq: Difference between revisions
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The | ==Cryo-EM structure of mouse BIRC6, Global map== | ||
<StructureSection load='8ivq' size='340' side='right'caption='[[8ivq]], [[Resolution|resolution]] 3.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ivq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IVQ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</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=8ivq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ivq OCA], [https://pdbe.org/8ivq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ivq RCSB], [https://www.ebi.ac.uk/pdbsum/8ivq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ivq ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions. | |||
Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.,Liu SS, Jiang TX, Bu F, Zhao JL, Wang GF, Yang GH, Kong JY, Qie YF, Wen P, Fan LB, Li NN, Gao N, Qiu XB Nat Commun. 2024 Jan 30;15(1):891. doi: 10.1038/s41467-024-45222-1. PMID:38291026<ref>PMID:38291026</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8ivq" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Bu F]] | |||
[[Category: Gao N]] | |||
[[Category: Jiang T]] | |||
[[Category: Li N]] | |||
[[Category: Liu S]] | |||
[[Category: Qiu X]] | |||
[[Category: Wang G]] | |||
[[Category: Zhao J]] | |||
Latest revision as of 12:44, 17 October 2024
Cryo-EM structure of mouse BIRC6, Global mapCryo-EM structure of mouse BIRC6, Global map
Structural highlights
Publication Abstract from PubMedProcaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions. Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.,Liu SS, Jiang TX, Bu F, Zhao JL, Wang GF, Yang GH, Kong JY, Qie YF, Wen P, Fan LB, Li NN, Gao N, Qiu XB Nat Commun. 2024 Jan 30;15(1):891. doi: 10.1038/s41467-024-45222-1. PMID:38291026[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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