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Open data
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Basic information
Entry | Database: PDB / ID: 7o2w | ||||||
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Title | Structure of the C9orf72-SMCR8 complex | ||||||
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![]() | PROTEIN BINDING / Denn domain / Coiled-coil / GTPase-activating protein | ||||||
Function / homology | ![]() SUMO is conjugated to E1 (UBA2:SAE1) / Atg1/ULK1 kinase complex / 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 ...SUMO is conjugated to E1 (UBA2:SAE1) / Atg1/ULK1 kinase complex / 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 / SUMOylation of DNA damage response and repair proteins / regulation of autophagosome assembly / negative regulation of autophagosome assembly / SUMOylation of DNA replication proteins / regulation of actin filament organization / septin ring / guanyl-nucleotide exchange factor complex / SUMOylation of SUMOylation proteins / negative regulation of immune response / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / SUMOylation of RNA binding proteins / axon extension / Flemming body / negative regulation of exocytosis / SUMOylation of chromatin organization proteins / positive regulation of autophagosome maturation / main axon / negative regulation of macroautophagy / detection of maltose stimulus / maltose transport complex / protein kinase inhibitor activity / ubiquitin-like protein ligase binding / carbohydrate transport / positive regulation of macroautophagy / protein sumoylation / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / positive regulation of TOR signaling / autophagosome / axonal growth cone / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / stress granule assembly / ATP-binding cassette (ABC) transporter complex / GTPase activator activity / guanyl-nucleotide exchange factor activity / cell chemotaxis / positive regulation of GTPase activity / negative regulation of protein phosphorylation / condensed nuclear chromosome / regulation of autophagy / cell projection / negative regulation of protein kinase activity / P-body / PML body / small GTPase binding / autophagy / cytoplasmic stress granule / endocytosis / protein tag activity / regulation of protein localization / presynapse / outer membrane-bounded periplasmic space / postsynapse / perikaryon / nuclear membrane / periplasmic space / lysosome / endosome / negative regulation of gene expression / intracellular membrane-bounded organelle / DNA damage response / dendrite / chromatin / protein kinase binding / extracellular space / nucleoplasm / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM | ||||||
![]() | Noerpel, J. / Cavadini, S. / Schenk, A.D. / Graff-Meyer, A. / Chao, J. / Bhaskar, V. | ||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 181.7 KB | Display | ![]() |
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PDB format | ![]() | 125.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 397.5 KB | Display | ![]() |
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Full document | ![]() | 425.6 KB | Display | |
Data in XML | ![]() | 23.4 KB | Display | |
Data in CIF | ![]() | 37.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 12700MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() Gene: SMT3, YDR510W, D9719.15, C9orf72 / Production host: ![]() ![]() |
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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.) ![]() ![]() ![]() Gene: SMCR8, malE, b4034, JW3994 / Production host: ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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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: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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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 | ||||||||||||||||||||||||
Refine LS restraints |
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