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- EMDB-17683: Neisseria meningitidis Type IV pilus SB-GATDH variant bound to th... -
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Open data
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Basic information
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Title | Neisseria meningitidis Type IV pilus SB-GATDH variant bound to the C24 nanobody | |||||||||
![]() | Raw map of the SB-GATDH variant of Neisseria meningitidis T4P bound to the C24 nanobody | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | helical reconstruction / ![]() | |||||||||
![]() | Fernandez-Martinez D / Dumenil G | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms. Authors: David Fernandez-Martinez / Youxin Kong / Sylvie Goussard / Agustin Zavala / Pauline Gastineau / Martial Rey / Gabriel Ayme / Julia Chamot-Rooke / Pierre Lafaye / Matthijn Vos / Ariel Mechaly ...Authors: David Fernandez-Martinez / Youxin Kong / Sylvie Goussard / Agustin Zavala / Pauline Gastineau / Martial Rey / Gabriel Ayme / Julia Chamot-Rooke / Pierre Lafaye / Matthijn Vos / Ariel Mechaly / Guillaume Duménil / ![]() Abstract: Type IV pili (T4P) are prevalent, polymeric surface structures in pathogenic bacteria, making them ideal targets for effective vaccines. However, bacteria have evolved efficient strategies to evade ...Type IV pili (T4P) are prevalent, polymeric surface structures in pathogenic bacteria, making them ideal targets for effective vaccines. However, bacteria have evolved efficient strategies to evade type IV pili-directed antibody responses. Neisseria meningitidis are prototypical type IV pili-expressing Gram-negative bacteria responsible for life threatening sepsis and meningitis. This species has evolved several genetic strategies to modify the surface of its type IV pili, changing pilin subunit amino acid sequence, nature of glycosylation and phosphoforms, but how these modifications affect antibody binding at the structural level is still unknown. Here, to explore this question, we determine cryo-electron microscopy (cryo-EM) structures of pili of different sequence types with sufficiently high resolution to visualize posttranslational modifications. We then generate nanobodies directed against type IV pili which alter pilus function in vitro and in vivo. Cyro-EM in combination with molecular dynamics simulation of the nanobody-pilus complexes reveals how the different types of pili surface modifications alter nanobody binding. Our findings shed light on the impressive complementarity between the different strategies used by bacteria to avoid antibody binding. Importantly, we also show that structural information can be used to make informed modifications in nanobodies as countermeasures to these immune evasion mechanisms. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 122.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19 KB 19 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.2 KB | Display | ![]() |
Images | ![]() | 41.3 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() ![]() | 216.8 MB 226.4 MB 226.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8pijMC ![]() 8p2vC ![]() 8p36C ![]() 8p3bC ![]() 8pizC ![]() 8pjpC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Raw map of the SB-GATDH variant of Neisseria meningitidis T4P bound to the C24 nanobody | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.93 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Additional map: DL sharpened map of the SB-GATDH variant of...
File | emd_17683_additional_1.map | ||||||||||||
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Annotation | DL sharpened map of the SB-GATDH variant of Neisseria meningitidis T4P bound to the C24 nanobody | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A of the SB-GATDH variant of...
File | emd_17683_half_map_1.map | ||||||||||||
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Annotation | Half map A of the SB-GATDH variant of Neisseria meningitidis T4P bound to the C24 nanobody | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B of the SB-GATDH variant of...
File | emd_17683_half_map_2.map | ||||||||||||
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Annotation | Half map B of the SB-GATDH variant of Neisseria meningitidis T4P bound to the C24 nanobody | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Complex of Neisseria meningitidis PilE SB-GATDH and the C24 nanobody
Entire | Name: Complex of Neisseria meningitidis PilE SB-GATDH and the C24 nanobody |
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Components |
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-Supramolecule #1: Complex of Neisseria meningitidis PilE SB-GATDH and the C24 nanobody
Supramolecule | Name: Complex of Neisseria meningitidis PilE SB-GATDH and the C24 nanobody type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Pilin
Macromolecule | Name: Pilin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.067182 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: FTLIELMIVI AIVGILAAVA LPAYQDYTAR AQVSEAILLA EGQKSAVTEY YLNHGEWPGD NSSAGVATSA DIKGKYVQSV TVANGVITA QMASSNVNNE IKSKKLSLWA KRQNGSVKWF CGQPVTRTTA TATDVAAANG KTDDKINTKH LPSTCRDDSS A S UniProtKB: ![]() |
-Macromolecule #2: C24 nanobody
Macromolecule | Name: C24 nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 13.911585 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MAQLQLVESG GGLVQPGGSL RLSCASSGFR SDYYAIVWFR QAPGKEREGV SCISTSGKTT IYADSVKGRF TISRDNAKNT VYLQMNSLK PEDTAVYYCA ADFRGSRLSD VCSYSSMDYW GKGTLATVS |
-Macromolecule #3: SN-GLYCEROL-3-PHOSPHATE
Macromolecule | Name: SN-GLYCEROL-3-PHOSPHATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: G3P |
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Molecular weight | Theoretical: 172.074 Da |
Chemical component information | ![]() ChemComp-G3P: |
-Macromolecule #4: (2~{R})-~{N}-[(2~{R},3~{S},4~{S},5~{R},6~{R})-5-acetamido-2-methy...
Macromolecule | Name: (2~{R})-~{N}-[(2~{R},3~{S},4~{S},5~{R},6~{R})-5-acetamido-2-methyl-4,6-bis(oxidanyl)oxan-3-yl]-2,3-bis(oxidanyl)propanamide type: ligand / ID: 4 / Number of copies: 1 / Formula: WKE |
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Molecular weight | Theoretical: 292.286 Da |
-Experimental details
-Structure determination
Method | ![]() |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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Refinement | Protocol: FLEXIBLE FIT |
Output model | ![]() PDB-8pij: |