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- EMDB-72382: Human antibody Fab MPV499 bound to hMPV DsCav-ES2 -

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Basic information

Entry
Database: EMDB / ID: EMD-72382
TitleHuman antibody Fab MPV499 bound to hMPV DsCav-ES2
Map data
Sample
  • Complex: Human antibody Fab MPV499 bound to hMPV DsCav-ES2
    • Protein or peptide: MPV499 bound to hMPV DsCav-Es2 F protein
Keywordsantibody / human metapneumovirus / ANTIVIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.57 Å
AuthorsEsfahani BG / Mousa J / Khalil AM
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01 AI143865 United States
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis for childhood antibody recognition of the human metapneumovirus fusion protein.
Authors: Ahmed Magdy Khalil / Behrouz Ghazi Esfahani / Rose J Miller / Jiachen Huang / Guillermina Kuan / Angel Balmaseda / Aubree Gordon / Jarrod J Mousa /
Abstract: Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and older adults, with most children becoming seropositive by five years of age. The hMPV fusion (F) ...Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and older adults, with most children becoming seropositive by five years of age. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while most common B-cell-targeted neutralizing epitopes on the hMPV F protein have been determined in hMPV-infected adults, the antibody response in hMPV-infected children remains undefined. We isolate five human monoclonal antibodies (mAbs) from hMPV-infected children, and evaluate their binding avidity, neutralization potency, epitope specificity, and in vivo efficacy. All mAbs are neutralizing, and epitope binning reveals four different epitopes targeted by the mAbs. Cryo-EM structures of four mAbs in complex with the hMPV F protein reveal epitopes on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determine the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. These findings provide new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAbs for hMPV F disease prevention.
History
DepositionAug 28, 2025-
Header (metadata) releaseSep 10, 2025-
Map releaseSep 10, 2025-
UpdateMar 18, 2026-
Current statusMar 18, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_72382.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.79 Å/pix.
x 340 pix.
= 268.6 Å
0.79 Å/pix.
x 340 pix.
= 268.6 Å
0.79 Å/pix.
x 340 pix.
= 268.6 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.79 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.2993481 - 0.6349319
Average (Standard dev.)0.0000016015553 (±0.021640755)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions340340340
Spacing340340340
CellA=B=C: 268.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_72382_additional_1.map
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Half map: #1

Fileemd_72382_half_map_1.map
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Half map: #2

Fileemd_72382_half_map_2.map
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Sample components

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Entire : Human antibody Fab MPV499 bound to hMPV DsCav-ES2

EntireName: Human antibody Fab MPV499 bound to hMPV DsCav-ES2
Components
  • Complex: Human antibody Fab MPV499 bound to hMPV DsCav-ES2
    • Protein or peptide: MPV499 bound to hMPV DsCav-Es2 F protein

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Supramolecule #1: Human antibody Fab MPV499 bound to hMPV DsCav-ES2

SupramoleculeName: Human antibody Fab MPV499 bound to hMPV DsCav-ES2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 90 KDa

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Macromolecule #1: MPV499 bound to hMPV DsCav-Es2 F protein

MacromoleculeName: MPV499 bound to hMPV DsCav-Es2 F protein / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYNWNWIR QHAGKGLEWI GYINYSGSTD YNPSLKSRVT ISVDTPKNQF SLKLTSVTAA DTAVYYCARG VDFWSGYCDY WGQGSLVTVS S PXXXXSLX VSPGERATLS CRASQSVGNN LAWYRQKPGQ APRLLIYGAS ...String:
QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYNWNWIR QHAGKGLEWI GYINYSGSTD YNPSLKSRVT ISVDTPKNQF SLKLTSVTAA DTAVYYCARG VDFWSGYCDY WGQGSLVTVS S PXXXXSLX VSPGERATLS CRASQSVGNN LAWYRQKPGQ APRLLIYGAS TRATGIPARF SGSGSGTEFT LTISSLQXED FAVYYCQQYD NWPPYTFGQG TKLEIK

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: DIRECT ELECTRON APOLLO (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: EMDB MAP
EMDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.57 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 22000
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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