+Open data
-Basic information
Entry | Database: PDB / ID: 6h03 | |||||||||
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Title | OPEN CONFORMATION OF THE MEMBRANE ATTACK COMPLEX | |||||||||
Components |
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Keywords | IMMUNE SYSTEM / C5B9 | |||||||||
Function / homology | Function and homology information cell killing / Terminal pathway of complement / membrane attack complex / complement binding / other organism cell membrane / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation / complement activation, alternative pathway / chemokine activity ...cell killing / Terminal pathway of complement / membrane attack complex / complement binding / other organism cell membrane / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation / complement activation, alternative pathway / chemokine activity / retinol binding / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production / complement activation, classical pathway / Peptide ligand-binding receptors / Regulation of Complement cascade / protein homooligomerization / chemotaxis / positive regulation of immune response / extracellular vesicle / G alpha (i) signalling events / in utero embryonic development / killing of cells of another organism / blood microparticle / cell surface receptor signaling pathway / inflammatory response / immune response / G protein-coupled receptor signaling pathway / innate immune response / signaling receptor binding / protein-containing complex binding / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.6 Å | |||||||||
Authors | Menny, A. / Serna, M. / Boyd, C.M. / Gardner, S. / Joseph, A.P. / Topf, M. / Bubeck, D. | |||||||||
Funding support | United Kingdom, 2items
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Citation | Journal: Nat Commun / Year: 2018 Title: CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers. Authors: Anaïs Menny / Marina Serna / Courtney M Boyd / Scott Gardner / Agnel Praveen Joseph / B Paul Morgan / Maya Topf / Nicholas J Brooks / Doryen Bubeck / Abstract: The membrane attack complex (MAC) is one of the immune system's first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of ...The membrane attack complex (MAC) is one of the immune system's first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant β-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how β-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions. | |||||||||
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 | 6h03.cif.gz | 2.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6h03.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6h03.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6h03_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
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Full document | 6h03_full_validation.pdf.gz | 3 MB | Display | |
Data in XML | 6h03_validation.xml.gz | 361.4 KB | Display | |
Data in CIF | 6h03_validation.cif.gz | 523.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h0/6h03 ftp://data.pdbj.org/pub/pdb/validation_reports/h0/6h03 | HTTPS FTP |
-Related structure data
Related structure data | 0106MC 0107C 0109C 0110C 0111C 0112C 0113C 6h04C 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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 177707.391 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01031 |
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-Complement component ... , 6 types, 23 molecules CDEFBGPHIJKLMNOQRSTUVWX
#2: Protein | Mass: 61122.852 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P07358 |
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#3: Protein | Mass: 91221.484 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P10643 |
#4: Protein | Mass: 20410.105 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P07360 |
#5: Protein | Mass: 61782.992 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P07357 |
#6: Protein | Mass: 102541.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P13671 |
#7: Protein | Mass: 61056.594 Da / Num. of mol.: 18 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P02748 |
-Sugars , 3 types, 58 molecules
#8: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||
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#9: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #10: Sugar | ChemComp-NAG / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (natural) |
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Buffer solution | pH: 7.4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 FIELD / Nominal magnification: 59000 X / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 2 sec. / Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON II (4k x 4k) / Num. of grids imaged: 8 / Num. of real images: 13009 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 288366 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 81968 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 5.6 Å |