+Open data
-Basic information
Entry | Database: PDB / ID: 8auk | ||||||
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Title | Cryo-EM structure of human BIRC6 in complex with HTRA2. | ||||||
Components |
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Keywords | LIGASE / E3 ubiquitin ligase / E2/E3 hybrid / inhibitor of apoptosis protein | ||||||
Function / homology | Function and homology information HtrA2 peptidase / pentacyclic triterpenoid metabolic process / negative regulation of mitophagy in response to mitochondrial depolarization / spongiotrophoblast layer development / positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / ceramide metabolic process / regulation of autophagy of mitochondrion / mitochondrial protein catabolic process / CD40 receptor complex / : ...HtrA2 peptidase / pentacyclic triterpenoid metabolic process / negative regulation of mitophagy in response to mitochondrial depolarization / spongiotrophoblast layer development / positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / ceramide metabolic process / regulation of autophagy of mitochondrion / mitochondrial protein catabolic process / CD40 receptor complex / : / labyrinthine layer development / ALK mutants bind TKIs / programmed cell death / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Flemming body / serine-type endopeptidase complex / adult walking behavior / response to herbicide / positive regulation of protein targeting to mitochondrion / execution phase of apoptosis / microtubule organizing center / cysteine-type endopeptidase inhibitor activity / positive regulation of execution phase of apoptosis / ubiquitin conjugating enzyme activity / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein autoprocessing / negative regulation of cell cycle / regulation of multicellular organism growth / neuron development / cellular response to interferon-beta / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / cellular response to retinoic acid / forebrain development / Mitochondrial protein degradation / serine-type peptidase activity / regulation of cytokinesis / mitochondrial membrane / negative regulation of extrinsic apoptotic signaling pathway / protein catabolic process / RING-type E3 ubiquitin transferase / trans-Golgi network / mitochondrial intermembrane space / cytoplasmic side of plasma membrane / cellular response to growth factor stimulus / spindle pole / ubiquitin-protein transferase activity / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by ALK fusions and activated point mutants / unfolded protein binding / peptidase activity / cellular response to heat / regulation of cell population proliferation / midbody / cellular response to oxidative stress / neuron apoptotic process / negative regulation of neuron apoptotic process / cell population proliferation / cytoskeleton / protein ubiquitination / endosome / positive regulation of apoptotic process / cell cycle / cell division / protein phosphorylation / serine-type endopeptidase activity / centrosome / apoptotic process / positive regulation of cell population proliferation / chromatin / endoplasmic reticulum membrane / negative regulation of apoptotic process / endoplasmic reticulum / mitochondrion / proteolysis / identical protein binding / membrane / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.2 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 | 8auk.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8auk.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8auk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8auk_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8auk_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8auk_validation.xml.gz | 168.4 KB | Display | |
Data in CIF | 8auk_validation.cif.gz | 257 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/au/8auk ftp://data.pdbj.org/pub/pdb/validation_reports/au/8auk | HTTPS FTP |
-Related structure data
Related structure data | 15672MC 8atuC 8atxC 8auwC 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: 35001.820 Da / Num. of mol.: 3 / Mutation: S306A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HTRA2, OMI, PRSS25 / Production host: Escherichia coli (E. coli) / References: UniProt: O43464, HtrA2 peptidase #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 HTRA2 homotrimer Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 1.17 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni, Escherichia coli |
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: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 15780 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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: 412.95 Å2 | ||||||||||||||||||||||||
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