+Open data
-Basic information
Entry | Database: PDB / ID: 8atu | ||||||
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Title | Cryo-EM structure of human BIRC6 | ||||||
Components | Baculoviral IAP repeat-containing protein 6 | ||||||
Keywords | LIGASE / E3 ubiquitin ligase / E2/E3 hybrid / inhibitor of apoptosis protein | ||||||
Function / homology | Function and homology information spongiotrophoblast layer development / labyrinthine layer development / ALK mutants bind TKIs / Flemming body / microtubule organizing center / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / RING-type E3 ubiquitin transferase ...spongiotrophoblast layer development / labyrinthine layer development / ALK mutants bind TKIs / Flemming body / microtubule organizing center / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / RING-type E3 ubiquitin transferase / trans-Golgi network / spindle pole / ubiquitin-protein transferase activity / Signaling by ALK fusions and activated point mutants / regulation of cell population proliferation / midbody / cell population proliferation / protein ubiquitination / endosome / cell cycle / cell division / protein phosphorylation / centrosome / apoptotic process / positive regulation of cell population proliferation / negative regulation of apoptotic process / membrane / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Ehrmann, J.F. / Grabarczyk, D.B. / Clausen, T. | ||||||
Funding support | European Union, 1items
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Citation | Journal: Science / Year: 2023 Title: Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex. Authors: Julian F Ehrmann / Daniel B Grabarczyk / Maria Heinke / Luiza Deszcz / Robert Kurzbauer / Otto Hudecz / Alexandra Shulkina / Rebeca Gogova / Anton Meinhart / Gijs A Versteeg / Tim Clausen / Abstract: Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally ...Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8atu.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8atu.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8atu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8atu_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8atu_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8atu_validation.xml.gz | 148.4 KB | Display | |
Data in CIF | 8atu_validation.cif.gz | 228.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/at/8atu ftp://data.pdbj.org/pub/pdb/validation_reports/at/8atu | HTTPS FTP |
-Related structure data
Related structure data | 15663MC 8atxC 8aukC 8auwC 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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1 |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: GLU / Beg label comp-ID: GLU / End auth comp-ID: ARG / End label comp-ID: ARG / Auth seq-ID: 54 - 4496 / Label seq-ID: 54 - 4496
NCS oper: (Code: givenMatrix: (-0.999999975918, 5.56777587321E-5, -0.000212283195748), (-5.57007101472E-5, -0.999999992605, 0.000108112587319), (-0.000212277174711, 0.00010812440904, 0.999999971624) ...NCS oper: (Code: given Matrix: (-0.999999975918, 5.56777587321E-5, -0.000212283195748), Vector: |
-Components
#1: Protein | Mass: 532009.000 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BIRC6, KIAA1289 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q9NR09, RING-type E3 ubiquitin transferase #2: Chemical | Has ligand of interest | N | |
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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: Human BIRC6 homodimer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 1.06 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 0.2 mg/ml / 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: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
Software |
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EM software | Name: RELION / Version: 4 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 136799 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL / Details: Alphafold2 | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 136.08 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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Refine LS restraints NCS | Type: NCS constraints / Rms dev position: 1.72024873981E-11 Å |