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- PDB-9c4f: Infectious B19V capsid -

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Basic information

Entry
Database: PDB / ID: 9c4f
TitleInfectious B19V capsid
Components
  • Capsid protein 2
  • Inter-alpha-trypsin inhibitor heavy chain H4
KeywordsVIRAL PROTEIN / B19 / Virion / Capsid
Function / homology
Function and homology information


hyaluronan metabolic process / platelet dense granule lumen / endopeptidase inhibitor activity / T=1 icosahedral viral capsid / response to cytokine / acute-phase response / serine-type endopeptidase inhibitor activity / Platelet degranulation / : / blood microparticle ...hyaluronan metabolic process / platelet dense granule lumen / endopeptidase inhibitor activity / T=1 icosahedral viral capsid / response to cytokine / acute-phase response / serine-type endopeptidase inhibitor activity / Platelet degranulation / : / blood microparticle / structural molecule activity / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Inter-alpha-trypsin inhibitor heavy chain, C-terminal / : / Inter-alpha-trypsin inhibitor heavy chain C-terminus / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP2 ...Inter-alpha-trypsin inhibitor heavy chain, C-terminal / : / Inter-alpha-trypsin inhibitor heavy chain C-terminus / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP2 / Capsid/spike protein, ssDNA virus / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily
Similarity search - Domain/homology
Inter-alpha-trypsin inhibitor heavy chain H4 / Capsid protein 2
Similarity search - Component
Biological speciesHuman parvovirus B19
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsLee, H. / Hafenstein, S.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2024
Title: Infectious parvovirus B19 circulates in the blood coated with active host protease inhibitors.
Authors: Hyunwook Lee / Ruben Assaraf / Suriyasri Subramanian / Dan Goetschius / Jan Bieri / Nadia M DiNunno / Remo Leisi / Carol M Bator / Susan L Hafenstein / Carlos Ros /
Abstract: The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure ...The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure (2.2 Å) of authentic B19V purified from a patient blood sample. There are significant differences compared to non-infectious VLPs. Most strikingly, two host protease inhibitors (PIs), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and serpinA3, were identified in complex with the capsids in all patient samples tested. The ITIH4 binds specifically to the icosahedral fivefold axis and serpinA3 occupies the twofold axis. The protein-coated virions remain infectious, and the capsid-associated PIs retain activity; however, upon virion interaction with target cells, the PIs dissociate from the capsid prior to viral entry. Our finding of an infectious virion shielded by bound host serum proteins suggests an evolutionarily favored phenomenon to evade immune surveillance and escape host protease activity.
History
DepositionJun 4, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Capsid protein 2
B: Capsid protein 2
E: Capsid protein 2
C: Capsid protein 2
D: Capsid protein 2
I: Inter-alpha-trypsin inhibitor heavy chain H4


Theoretical massNumber of molelcules
Total (without water)408,0506
Polymers408,0506
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein
Capsid protein 2 / Capsid protein VP2 / VP2 / VP2 protein


Mass: 60916.016 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Source: (natural) Human parvovirus B19 / References: UniProt: Q784T0
#2: Protein Inter-alpha-trypsin inhibitor heavy chain H4 / ITI heavy chain H4 / ITI-HC4 / Inter-alpha-inhibitor heavy chain 4 / Inter-alpha-trypsin inhibitor ...ITI heavy chain H4 / ITI-HC4 / Inter-alpha-inhibitor heavy chain 4 / Inter-alpha-trypsin inhibitor family heavy chain-related protein / IHRP / Plasma kallikrein sensitive glycoprotein 120 / Gp120 / PK-120


Mass: 103470.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14624
Has protein modificationN

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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
1Human parvovirus B19 with inter-alpha-trypsin inhibitor heavy chain H4COMPLEXall0MULTIPLE SOURCES
2Human parvovirus B19VIRUS#11NATURAL
3Inter-alpha-trypsin inhibitor heavy chain H4COMPLEX#21NATURAL
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Human parvovirus B1910798
33Homo sapiens (human)9606
Details of virusEmpty: NO / Enveloped: NO / Isolate: SEROTYPE / Type: VIRION
Buffer solutionpH: 7
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: 3000 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 100 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 192181
Details: C1 reconstruction was performed by using ISECC with selected particles from subparticle analysis
Symmetry type: POINT

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