+Open data
-Basic information
Entry | Database: PDB / ID: 8ivq | ||||||
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Title | Cryo-EM structure of mouse BIRC6, Global map | ||||||
Components | Isoform 2 of Baculoviral IAP repeat-containing protein 6 | ||||||
Keywords | APOPTOSIS / Inhibitor of apoptosis protein / BIRC6 / Smac | ||||||
Function / homology | Function and homology information spongiotrophoblast layer development / labyrinthine layer development / Flemming body / microtubule organizing center / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / trans-Golgi network / RING-type E3 ubiquitin transferase ...spongiotrophoblast layer development / labyrinthine layer development / Flemming body / microtubule organizing center / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / trans-Golgi network / RING-type E3 ubiquitin transferase / placenta development / spindle pole / regulation of cell population proliferation / midbody / cell population proliferation / endosome / protein ubiquitination / cell division / centrosome / positive regulation of cell population proliferation / negative regulation of apoptotic process / apoptotic process / membrane / nucleus Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Liu, S. / Jiang, T. / Bu, F. / Zhao, J. / Wang, G. / Li, N. / Gao, N. / Qiu, X. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy. Authors: Shuo-Shuo Liu / Tian-Xia Jiang / Fan Bu / Ji-Lan Zhao / Guang-Fei Wang / Guo-Heng Yang / Jie-Yan Kong / Yun-Fan Qie / Pei Wen / Li-Bin Fan / Ning-Ning Li / Ning Gao / Xiao-Bo Qiu / Abstract: 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 ...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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ivq.cif.gz | 1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8ivq.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8ivq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ivq_validation.pdf.gz | 436.6 KB | Display | wwPDB validaton report |
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Full document | 8ivq_full_validation.pdf.gz | 469.7 KB | Display | |
Data in XML | 8ivq_validation.xml.gz | 99.8 KB | Display | |
Data in CIF | 8ivq_validation.cif.gz | 154.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/iv/8ivq ftp://data.pdbj.org/pub/pdb/validation_reports/iv/8ivq | HTTPS FTP |
-Related structure data
Related structure data | 35759MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 535020.812 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: The plasmid used for BIRC6 protein expression in this deposition is originated from Dr. Stefan Jentsch lab, and the Birc6 sequence in that plasmid is available from GenBank under accession ...Details: The plasmid used for BIRC6 protein expression in this deposition is originated from Dr. Stefan Jentsch lab, and the Birc6 sequence in that plasmid is available from GenBank under accession number GenBank: Y17267.1. No identical sequence could be identified in Uniprot. Here is the citation of the used Birc6 sequence: Hauser, H.P., et al., A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. Journal of Cell Biology, 1998. 141(6): p. 1415-1422. Source: (gene. exp.) Mus musculus (house mouse) / Gene: Birc6, Kiaa1289 / Production host: Homo sapiens (human) References: UniProt: O88738, RING-type E3 ubiquitin transferase Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Baculoviral IAP repeat-containing protein 6, Dimer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 2000 nm |
Image recording | Electron dose: 68.4 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 154000 / Symmetry type: POINT | ||||||||||||||||||||||||
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