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- PDB-8ygu: Cryo-EM structure of simian rotavirus SA11 VP4 in complex with nA... -

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Basic information

Entry
Database: PDB / ID: 8ygu
TitleCryo-EM structure of simian rotavirus SA11 VP4 in complex with nAb 7H13-I54G mutant (right side)
Components
  • (Outer capsid protein VP4) x 2
  • Antibody 7H13-I54G mutant heavy chain
  • Antibody 7H13-I54G mutant light chain
KeywordsVIRUS / ROTAVIRUS / VP4 / 7H13
Function / homology
Function and homology information


host cytoskeleton / viral outer capsid / symbiont entry into host cell via permeabilization of host membrane / host cell endoplasmic reticulum / virion attachment to host cell / host cell plasma membrane / membrane
Similarity search - Function
Rotavirus VP4 helical domain / Rotavirus VP4 helical domain / Outer capsid protein VP4 / Rotavirus VP4, membrane interaction domain superfamily / Rotavirus VP4, membrane interaction domain / Rotavirus VP4 membrane interaction domain / Haemagglutinin outer capsid protein VP4, concanavalin-like domain / Outer Capsid protein VP4 (Hemagglutinin) Concanavalin-like domain / Concanavalin A-like lectin/glucanase domain superfamily
Similarity search - Domain/homology
Outer capsid protein VP4
Similarity search - Component
Biological speciesMus musculus (house mouse)
Rotavirus A
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.13 Å
AuthorsHuang, Y. / Sun, H. / Zheng, Q. / Li, S. / Ge, S. / Xia, N.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2025
Title: A single residue switch mediates the broad neutralization of Rotaviruses.
Authors: Yang Huang / Feibo Song / Yuanjun Zeng / Hui Sun / Roufang Sheng / Xuechun Wang / Liqin Liu / Guoxing Luo / Yanan Jiang / Yaling Chen / Mengxuan Zhang / Shiyin Zhang / Ying Gu / Hai Yu / ...Authors: Yang Huang / Feibo Song / Yuanjun Zeng / Hui Sun / Roufang Sheng / Xuechun Wang / Liqin Liu / Guoxing Luo / Yanan Jiang / Yaling Chen / Mengxuan Zhang / Shiyin Zhang / Ying Gu / Hai Yu / Shaowei Li / Tingdong Li / Qingbing Zheng / Shengxiang Ge / Jun Zhang / Ningshao Xia /
Abstract: Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing ...Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing challenge posed by viral evolution and immune evasion intensifies the importance of the discovery of bNAbs and their underlying neutralization mechanism. Here, focusing on the pivotal viral protein VP4 of rotavirus (RV), we identify a potent bNAb, 7H13, exhibiting broad-spectrum neutralization across diverse RV genotypes and demonstrating strong prevention of virus infection in female mice. A combination of time-resolved cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) analysis reveals a counterintuitive dynamic process of virus inactivation, in which 7H13 asymmetrically binds to a conserved epitope in the capsid-proximal aspect of VP4, triggers a conformational switch in a critical residue-F418-thereby disrupts the meta-stable conformation of VP4 essential for normal viral infection. Structure-guided mutagenesis corroborates the essential role of the 7H13 heavy chain I54 in activating F418 switch and destabilizing VP4. These findings define an atypical NAbs' neutralization mechanism and reveal a potential type of virus vulnerable site for universal vaccine and therapeutics design.
History
DepositionFeb 27, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Feb 12, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Outer capsid protein VP4
B: Outer capsid protein VP4
C: Outer capsid protein VP4
H: Antibody 7H13-I54G mutant heavy chain
L: Antibody 7H13-I54G mutant light chain


Theoretical massNumber of molelcules
Total (without water)263,5075
Polymers263,5075
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Outer capsid protein VP4


Mass: 87147.477 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Rotavirus A / Strain: SA11 / References: UniProt: A0A5J6BC68
#2: Protein Outer capsid protein VP4


Mass: 64861.418 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Rotavirus A / Strain: SA11 / References: UniProt: A0A5J6BC68
#3: Antibody Antibody 7H13-I54G mutant heavy chain


Mass: 12710.160 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#4: Antibody Antibody 7H13-I54G mutant light chain


Mass: 11640.938 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Immune complex of rotavirus with 7H13-I54G mutantCOMPLEXall0MULTIPLE SOURCES
2Rotavirus VP4COMPLEX#1-#21NATURAL
3Fab 7H13COMPLEX#3-#41RECOMBINANT
Molecular weight
IDEntity assembly-IDExperimental value
11NO
22
31NO
43
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-IDStrain
21Rotavirus A28875SA11
32Rotavirus A28875SA11
43Rotavirus A28875SA11
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
11Homo sapiens (human)9606
23Homo sapiens (human)9606
Details of virusEmpty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 300 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.13 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 280420 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0063783
ELECTRON MICROSCOPYf_angle_d0.8585133
ELECTRON MICROSCOPYf_dihedral_angle_d4.1812196
ELECTRON MICROSCOPYf_chiral_restr0.057565
ELECTRON MICROSCOPYf_plane_restr0.007653

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