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Open data
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Basic information
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Title | Fab 77-stabilized MeV F ectodomain fragment | ||||||||||||||||||
![]() | local filtered map | ||||||||||||||||||
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![]() | VIRAL PROTEIN / glycoprotein / immune system / antibody / measles / high-resolution / antibody fragment / fab / neutralizing antibody / ectodomain | ||||||||||||||||||
Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0![]() | ||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||||||||
![]() | Zyla D / Saphire EO | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: A neutralizing antibody prevents postfusion transition of measles virus fusion protein. Authors: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben ...Authors: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben Parekh / Tara C Marcink / Ruben Diaz Avalos / Branka Horvat / Cyrille Mathieu / Joost Snijder / Alexander L Greninger / Kathryn M Hastie / Stefan Niewiesk / Anne Moscona / Matteo Porotto / Erica Ollmann Saphire / ![]() ![]() ![]() ![]() ![]() Abstract: Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be ...Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 301.3 KB | ![]() | |
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Header (meta data) | ![]() ![]() | 25.7 KB 25.7 KB | Display Display | ![]() |
Images | ![]() | 47.1 KB | ||
Masks | ![]() | 15.6 MB | ![]() | |
Filedesc metadata | ![]() | 7.5 KB | ||
Others | ![]() ![]() ![]() | 14.7 MB 14.5 MB 14.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 628.3 KB | Display | ![]() |
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Full document | ![]() | 627.9 KB | Display | |
Data in XML | ![]() | 9.5 KB | Display | |
Data in CIF | ![]() | 11.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9at8MC ![]() 8ut2C ![]() 8utfC ![]() 8uupC ![]() 8uuqC M: atomic model generated by this map C: citing same article ( |
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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 | local filtered map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.403 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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-Additional map: sharpened map
File | emd_43827_additional_1.map | ||||||||||||
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Annotation | sharpened map | ||||||||||||
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-Half map: half-map 1
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Annotation | half-map 1 | ||||||||||||
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-Half map: half-map 2
File | emd_43827_half_map_2.map | ||||||||||||
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Annotation | half-map 2 | ||||||||||||
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Sample components
-Entire : Fab 77-stabilized MeV F ectodomain fragment
Entire | Name: Fab 77-stabilized MeV F ectodomain fragment |
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Components |
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-Supramolecule #1: Fab 77-stabilized MeV F ectodomain fragment
Supramolecule | Name: Fab 77-stabilized MeV F ectodomain fragment / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: last refolding step of F ectodomain refolding in the presence of mAb 77 |
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Molecular weight | Theoretical: 43 KDa |
-Supramolecule #2: Antibody 77 Fab Heavy Chain, Antibody 77 Fab Light Chain
Supramolecule | Name: Antibody 77 Fab Heavy Chain, Antibody 77 Fab Light Chain type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: Measles virus Fusion glycoprotein
Supramolecule | Name: Measles virus Fusion glycoprotein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Fusion glycoprotein F0
Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 57.379539 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGLKVNVSAI FMAVLLTLQT PTGQIHWGNL SKIGVVGIGS ASYKVMTRSS HQSLVIKLMP NITLLNNCTR VEIAEYRRLL RTVLEPIRD ALNAMTQNIR PVQSVASSRR HKRFAGVVLA GAALGVATAA QITAGIALHQ SMLNSQAIDN LRASLETTNQ A IEAIRQAG ...String: MGLKVNVSAI FMAVLLTLQT PTGQIHWGNL SKIGVVGIGS ASYKVMTRSS HQSLVIKLMP NITLLNNCTR VEIAEYRRLL RTVLEPIRD ALNAMTQNIR PVQSVASSRR HKRFAGVVLA GAALGVATAA QITAGIALHQ SMLNSQAIDN LRASLETTNQ A IEAIRQAG QGMILAVQGV QDYINNELIP SMNQLSCDLI GQKLGLKLLR YYTEILSLFG PSLRDPISAE ISIQALSYAL GG DINKVLE KLGYSGGDLL GILESRGIKA RITHVDTESY FIVLSIAYPT LSEIKGVIVH RLEGVSYNIG SQEWYTTVPK YVA TQGYLI SNFDESSCTF MPEGTVCSQN ALYPMSPLLQ ECLRGSTKSC ARTLVSGSFG NRFILSQGNL IANCASILCK CYTT GTIIN QDPDKILTYI AADHCPVVEV NGVTIQVGSR RYPDAVYLHR IDLGPPISLG RLDVGTNLGN AIAKLEDAKE LLESS DQIL RSMKGLSSTS IGVDDDDKAG WSHPQFEKGG GSGGGSGGGS WSHPQFEK UniProtKB: Fusion glycoprotein F0 |
-Macromolecule #2: mAb 77 light chain
Macromolecule | Name: mAb 77 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.532512 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGWSCIILFL VATATGVHSD VQITQSPSYL AASPGETITI NCRASKSISK YLAWYQEKPG KTNELLIYSG STLQSGIPSR FRGSGSGTD FTLTISSLEP EDFAMYYCQQ HNEYTLTFGG GTKLELKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK ...String: MGWSCIILFL VATATGVHSD VQITQSPSYL AASPGETITI NCRASKSISK YLAWYQEKPG KTNELLIYSG STLQSGIPSR FRGSGSGTD FTLTISSLEP EDFAMYYCQQ HNEYTLTFGG GTKLELKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC |
-Macromolecule #3: mAB 77 heavy chain
Macromolecule | Name: mAB 77 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 52.722336 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGWSCIILFL VATATGVHSD VQLQESGPGL VKPSQSLSLT CTVSGYSITS DYAWNWIRQF PGNKLEWMGY ISYTLTTGYN PSLKSRISI TRDSSKNQFF LQLNSVTTED TATYYCARSG WLLPYWYFDV WGAGTTVTVS SASTKGPSVF PLAPSSKSTS G GTAALGCL ...String: MGWSCIILFL VATATGVHSD VQLQESGPGL VKPSQSLSLT CTVSGYSITS DYAWNWIRQF PGNKLEWMGY ISYTLTTGYN PSLKSRISI TRDSSKNQFF LQLNSVTTED TATYYCARSG WLLPYWYFDV WGAGTTVTVS SASTKGPSVF PLAPSSKSTS G GTAALGCL VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EP KSCDKGL EVLFQGPTHT CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH NAK TKPREE QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS RDELTKNQVS LTCL VKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 8 / Details: HEPES 50 mM, pH 8.0, NaCl 150 mM |
Grid | Model: Quantifoil / Material: COPPER / Mesh: 300 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 4 / Number real images: 10344 / Average exposure time: 2.0 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |