+Open data
-Basic information
Entry | Database: PDB / ID: 7o2w | ||||||
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Title | Structure of the C9orf72-SMCR8 complex | ||||||
Components |
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Keywords | PROTEIN BINDING / Denn domain / Coiled-coil / GTPase-activating protein | ||||||
Function / homology | Function and homology information Atg1/ULK1 kinase complex / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / late endosome to lysosome transport / SUMOylation of transcription cofactors / regulation of TORC1 signaling ...Atg1/ULK1 kinase complex / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / late endosome to lysosome transport / SUMOylation of transcription cofactors / regulation of TORC1 signaling / septin ring / SUMOylation of DNA damage response and repair proteins / SUMOylation of SUMOylation proteins / regulation of autophagosome assembly / negative regulation of autophagosome assembly / SUMOylation of DNA replication proteins / regulation of actin filament organization / guanyl-nucleotide exchange factor complex / SUMOylation of RNA binding proteins / negative regulation of immune response / SUMOylation of chromatin organization proteins / axon extension / negative regulation of exocytosis / Flemming body / positive regulation of autophagosome maturation / main axon / negative regulation of macroautophagy / detection of maltose stimulus / maltose binding / maltose transport complex / protein kinase inhibitor activity / maltose transport / maltodextrin transmembrane transport / ubiquitin-like protein ligase binding / positive regulation of macroautophagy / protein sumoylation / carbohydrate transport / carbohydrate transmembrane transporter activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / positive regulation of TOR signaling / autophagosome / axonal growth cone / stress granule assembly / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / GTPase activator activity / guanyl-nucleotide exchange factor activity / negative regulation of protein phosphorylation / condensed nuclear chromosome / regulation of autophagy / cell projection / P-body / negative regulation of protein kinase activity / small GTPase binding / autophagy / positive regulation of GTPase activity / protein tag activity / cytoplasmic stress granule / endocytosis / regulation of protein localization / presynapse / outer membrane-bounded periplasmic space / perikaryon / postsynapse / nuclear membrane / lysosome / periplasmic space / endosome / negative regulation of gene expression / intracellular membrane-bounded organelle / dendrite / DNA damage response / chromatin / protein kinase binding / extracellular space / nucleoplasm / membrane / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Saccharomyces cerevisiae S288c (yeast) Homo sapiens (human) Escherichia coli K-12 (bacteria) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM | ||||||
Authors | Noerpel, J. / Cavadini, S. / Schenk, A.D. / Graff-Meyer, A. / Chao, J. / Bhaskar, V. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: PLoS Biol / Year: 2021 Title: Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture. Authors: Julia Nörpel / Simone Cavadini / Andreas D Schenk / Alexandra Graff-Meyer / Daniel Hess / Jan Seebacher / Jeffrey A Chao / Varun Bhaskar / Abstract: A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2 repeat expansion in the first intron of the C9orf72 gene. ...A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2 repeat expansion in the first intron of the C9orf72 gene. Many underlying mechanisms lead to manifestation of disease that include toxic gain-of-function by repeat G4C2 RNAs, dipeptide repeat proteins, and a reduction of the C9orf72 gene product. The C9orf72 protein interacts with SMCR8 and WDR41 to form a trimeric complex and regulates multiple cellular pathways including autophagy. Here, we report the structure of the C9orf72-SMCR8 complex at 3.8 Å resolution using single-particle cryo-electron microscopy (cryo-EM). The structure reveals 2 distinct dimerization interfaces between C9orf72 and SMCR8 that involves an extensive network of interactions. Homology between C9orf72-SMCR8 and Folliculin-Folliculin Interacting Protein 2 (FLCN-FNIP2), a GTPase activating protein (GAP) complex, enabled identification of a key residue within the active site of SMCR8. Further structural analysis suggested that a coiled-coil region within the uDenn domain of SMCR8 could act as an interaction platform for other coiled-coil proteins, and its deletion reduced the interaction of the C9orf72-SMCR8 complex with FIP200 upon starvation. In summary, this study contributes toward our understanding of the biological function of the C9orf72-SMCR8 complex. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7o2w.cif.gz | 175.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7o2w.ent.gz | 128.7 KB | Display | PDB format |
PDBx/mmJSON format | 7o2w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o2/7o2w ftp://data.pdbj.org/pub/pdb/validation_reports/o2/7o2w | HTTPS FTP |
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-Related structure data
Related structure data | 12700MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 67167.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Saccharomyces cerevisiae S288c (yeast), (gene. exp.) Homo sapiens (human) Gene: SMT3, YDR510W, D9719.15, C9orf72 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q12306, UniProt: Q96LT7 |
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#2: Protein | Mass: 134389.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Escherichia coli K-12 (bacteria) Gene: SMCR8, malE, b4034, JW3994 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8TEV9, UniProt: P0AEX9 |
-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: C9orf72-SMCR8 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.201 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.37 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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Num. of particles: 284568 / Symmetry type: POINT | ||||||||||||||||||||||||
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