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Structure paper

TitleIntegrated cryoEM structure of a spumaretrovirus reveals cross-kingdom evolutionary relationships and the molecular basis for assembly and virus entry.
Journal, issue, pagesCell, Year 2024
Publish dateJul 6, 2024
AuthorsThomas Calcraft / Nicole Stanke-Scheffler / Andrea Nans / Dirk Lindemann / Ian A Taylor / Peter B Rosenthal /
PubMed AbstractFoamy viruses (FVs) are an ancient lineage of retroviruses, with an evolutionary history spanning over 450 million years. Vector systems based on Prototype Foamy Virus (PFV) are promising candidates ...Foamy viruses (FVs) are an ancient lineage of retroviruses, with an evolutionary history spanning over 450 million years. Vector systems based on Prototype Foamy Virus (PFV) are promising candidates for gene and oncolytic therapies. Structural studies of PFV contribute to the understanding of the mechanisms of FV replication, cell entry and infection, and retroviral evolution. Here we combine cryoEM and cryoET to determine high-resolution in situ structures of the PFV icosahedral capsid (CA) and envelope glycoprotein (Env), including its type III transmembrane anchor and membrane-proximal external region (MPER), and show how they are organized in an integrated structure of assembled PFV particles. The atomic models reveal an ancient retroviral capsid architecture and an unexpected relationship between Env and other class 1 fusion proteins of the Mononegavirales. Our results represent the de novo structure determination of an assembled retrovirus particle.
External linksCell / PubMed:39013471
MethodsEM (single particle) / EM (subtomogram averaging) / EM (tomography)
Resolution3.4 - 13.5 Å
Structure data

EMDB-17311, PDB-8ozj:
In situ cryoEM structure of Prototype Foamy Virus Env dimer of trimers
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-17312, PDB-8ozk:
In situ cryoEM structure of the Prototype Foamy Virus capsid, icosahedral map
Method: EM (single particle) / Resolution: 3.89 Å

EMDB-17313, PDB-8ozl:
In situ cryoEM structure of the Prototype Foamy Virus capsid, pentamer localised reconstruction
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-17314, PDB-8ozm:
In situ cryoEM structure of the Prototype Foamy Virus capsid, hexamer 1 localised reconstruction
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-17315, PDB-8ozn:
In situ cryoEM structure of the Prototype Foamy Virus capsid, hexamer 2 localised reconstruction
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-17316: In situ subtomogram average of Prototype Foamy Virus Env trimer
Method: EM (subtomogram averaging) / Resolution: 4.9 Å

EMDB-17317, PDB-8ozp:
In situ subtomogram average of Prototype Foamy Virus Env pentamer of trimers
Method: EM (subtomogram averaging) / Resolution: 11.9 Å

EMDB-17318, PDB-8ozq:
In situ subtomogram average of Prototype Foamy Virus Env hexamer of trimers
Method: EM (subtomogram averaging) / Resolution: 10.0 Å

EMDB-17319: In situ subtomogram average of the Prototype Foamy Virus capsid, wild-type Gag
Method: EM (subtomogram averaging) / Resolution: 10.2 Å

EMDB-17320: In situ subtomogram average of the Prototype Foamy Virus capsid, p68 Gag
Method: EM (subtomogram averaging) / Resolution: 13.5 Å

EMDB-17321: Cryotomogram of Prototype Foamy Virus particles, wild-type Gag
Method: EM (tomography)

EMDB-17322: Cryotomogram of Prototype Foamy Virus particles, p68 Gag
Method: EM (tomography)

Chemicals

ChemComp-CLR:
CHOLESTEROL

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • eastern chimpanzee simian foamy virus
KeywordsVIRAL PROTEIN / membrane fusion / envelope glycoprotein / foamy virus / MPER / transmembrane / MEMBRANE PROTEIN / capsid / Gag / pentamer / hexamer

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