+Open data
-Basic information
Entry | Database: PDB / ID: 8f2r | ||||||||||||||||||||||||||||||
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Title | Human CCC complex | ||||||||||||||||||||||||||||||
Components | (COMM domain-containing protein ...) x 10 | ||||||||||||||||||||||||||||||
Keywords | ENDOCYTOSIS / endosomal sorting / commander / CCC complex | ||||||||||||||||||||||||||||||
Function / homology | Function and homology information negative regulation of sodium ion transmembrane transport / plasma membrane to endosome transport / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein localization to cell surface / copper ion homeostasis / Golgi to plasma membrane transport / phosphatidic acid binding / sodium channel inhibitor activity / phosphatidylinositol-3,4-bisphosphate binding / phosphatidylinositol-3,5-bisphosphate binding ...negative regulation of sodium ion transmembrane transport / plasma membrane to endosome transport / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein localization to cell surface / copper ion homeostasis / Golgi to plasma membrane transport / phosphatidic acid binding / sodium channel inhibitor activity / phosphatidylinositol-3,4-bisphosphate binding / phosphatidylinositol-3,5-bisphosphate binding / Cul2-RING ubiquitin ligase complex / negative regulation of NF-kappaB transcription factor activity / sodium ion transport / phosphatidylinositol-3,4,5-trisphosphate binding / NF-kappaB binding / phosphatidylinositol-4,5-bisphosphate binding / tumor necrosis factor-mediated signaling pathway / cholesterol homeostasis / positive regulation of protein ubiquitination / nucleotide-excision repair / recycling endosome / protein transport / Neddylation / cytoplasmic vesicle / secretory granule lumen / ficolin-1-rich granule lumen / early endosome / endosome membrane / endosome / copper ion binding / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / Neutrophil degranulation / Golgi apparatus / protein homodimerization activity / extracellular region / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.12 Å | ||||||||||||||||||||||||||||||
Authors | Healy, M.D. / McNally, K.E. / Butkovic, R. / Chilton, M. / Kato, K. / Sacharz, J. / McConville, C. / Moody, E.R.R. / Shaw, S. / Planelles-Herrero, V.J. ...Healy, M.D. / McNally, K.E. / Butkovic, R. / Chilton, M. / Kato, K. / Sacharz, J. / McConville, C. / Moody, E.R.R. / Shaw, S. / Planelles-Herrero, V.J. / Kadapalakere, S.Y. / Ross, J. / Borucu, U. / Palmer, C.S. / Chen, K. / Croll, T.I. / Hall, R.J. / Caruana, N.J. / Ghai, R. / Nguyen, T.H.D. / Heesom, K.J. / Saitoh, S. / Berger, I. / Berger-Schaffitzel, C. / Williams, T.A. / Stroud, D.A. / Derivery, E. / Collins, B.M. / Cullen, P.J. | ||||||||||||||||||||||||||||||
Funding support | United Kingdom, Australia, 9items
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Citation | Journal: Cell / Year: 2023 Title: Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome. Authors: Michael D Healy / Kerrie E McNally / Rebeka Butkovič / Molly Chilton / Kohji Kato / Joanna Sacharz / Calum McConville / Edmund R R Moody / Shrestha Shaw / Vicente J Planelles-Herrero / ...Authors: Michael D Healy / Kerrie E McNally / Rebeka Butkovič / Molly Chilton / Kohji Kato / Joanna Sacharz / Calum McConville / Edmund R R Moody / Shrestha Shaw / Vicente J Planelles-Herrero / Sathish K N Yadav / Jennifer Ross / Ufuk Borucu / Catherine S Palmer / Kai-En Chen / Tristan I Croll / Ryan J Hall / Nikeisha J Caruana / Rajesh Ghai / Thi H D Nguyen / Kate J Heesom / Shinji Saitoh / Imre Berger / Christiane Schaffitzel / Tom A Williams / David A Stroud / Emmanuel Derivery / Brett M Collins / Peter J Cullen / Abstract: The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, ...The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery. | ||||||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8f2r.cif.gz | 604.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f2r.ent.gz | 503.4 KB | Display | PDB format |
PDBx/mmJSON format | 8f2r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8f2r_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8f2r_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8f2r_validation.xml.gz | 64 KB | Display | |
Data in CIF | 8f2r_validation.cif.gz | 95.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f2/8f2r ftp://data.pdbj.org/pub/pdb/validation_reports/f2/8f2r | HTTPS FTP |
-Related structure data
Related structure data | 28825MC 8esdC 8eseC 8f2uC 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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-Components
-COMM domain-containing protein ... , 10 types, 10 molecules ABCDEFGHIJ
#1: Protein | Mass: 20863.715 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD1, C2orf5, MURR1 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q8N668 |
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#2: Protein | Mass: 22776.113 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD2, HSPC042, My004 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q86X83 |
#3: Protein | Mass: 22179.117 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD3, BUP, C10orf8 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9UBI1 |
#4: Protein | Mass: 21790.354 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD4 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9H0A8 |
#5: Protein | Mass: 22779.260 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD5, HT002 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9GZQ3 |
#6: Protein | Mass: 8819.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD6, MSTP076 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q7Z4G1 |
#7: Protein | Mass: 22561.953 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD7, C20orf92 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q86VX2 |
#8: Protein | Mass: 20629.801 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD8, MDS022 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9NX08 |
#9: Protein | Mass: 21844.117 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD9, HSPC166 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9P000 |
#10: Protein | Mass: 22596.881 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COMMD10, HSPC305, PTD002 / Cell line (production host): Sf21 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q9Y6G5 |
-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 CCC complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera (butterflies/moths) / Strain: Sf21 |
Buffer solution | pH: 7.2 Details: 50 mM HEPES pH7.2, 150 mM NaCl, 2mM beta-mercaptoethanol, 0.01% Triton-X100 |
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Human CCC complex cross-linked with 1 mM BS3 |
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / 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: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Average exposure time: 9.01 sec. / Electron dose: 43.14 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 5651 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 153104 / Symmetry type: POINT |