+Open data
-Basic information
Entry | Database: PDB / ID: 8auw | ||||||
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Title | Cryo-EM structure of human BIRC6 in complex with SMAC. | ||||||
Components |
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Keywords | LIGASE / E3 ubiquitin ligase / E2/E3 hybrid / inhibitor of apoptosis protein | ||||||
Function / homology | Function and homology information activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / spongiotrophoblast layer development / Release of apoptotic factors from the mitochondria / CD40 receptor complex / labyrinthine layer development / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Flemming body / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs ...activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / spongiotrophoblast layer development / Release of apoptotic factors from the mitochondria / CD40 receptor complex / labyrinthine layer development / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Flemming body / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / microtubule organizing center / intrinsic apoptotic signaling pathway in response to oxidative stress / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / extrinsic apoptotic signaling pathway via death domain receptors / intrinsic apoptotic signaling pathway / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / trans-Golgi network / RING-type E3 ubiquitin transferase / mitochondrial intermembrane space / cytoplasmic side of plasma membrane / activation of cysteine-type endopeptidase activity involved in apoptotic process / spindle pole / ubiquitin-protein transferase activity / Signaling by ALK fusions and activated point mutants / regulation of cell population proliferation / midbody / neuron apoptotic process / cell population proliferation / endosome / protein ubiquitination / positive regulation of apoptotic process / protein phosphorylation / cell division / centrosome / positive regulation of cell population proliferation / negative regulation of apoptotic process / apoptotic process / mitochondrion / membrane / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.2 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 | 8auw.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8auw.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8auw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8auw_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8auw_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8auw_validation.xml.gz | 157.1 KB | Display | |
Data in CIF | 8auw_validation.cif.gz | 242.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/au/8auw ftp://data.pdbj.org/pub/pdb/validation_reports/au/8auw | HTTPS FTP |
-Related structure data
Related structure data | 15675MC 8atuC 8atxC 8aukC C: citing same article (ref.) M: map data used to model this data |
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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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-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: Protein | Mass: 20787.098 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DIABLO, SMAC / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NR28 #3: 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 in complex with SMAC homodimer / Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 1.1 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: 1500 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: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 7.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56954 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL / Details: Alphafold2 | ||||||||||||||||||||||||
Atomic model building |
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Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 527.72 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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