10779/crick.12588962.v1
Neil J Ball
Neil J
Ball
Giuseppe Nicastro
Giuseppe
Nicastro
Moumita Dutta
Moumita
Dutta
Dominic J Pollard
Dominic J
Pollard
David C Goldstone
David C
Goldstone
Marta Sanz-Ramos
Marta
Sanz-Ramos
Andres Ramos
Andres
Ramos
Erik Müllers
Erik
Müllers
Kristin Stirnnagel
Kristin
Stirnnagel
Nicole Stanke
Nicole
Stanke
Dirk Lindemann
Dirk
Lindemann
Jonathan P Stoye
Jonathan P
Stoye
William R Taylor
William R
Taylor
Peter B Rosenthal
Peter B
Rosenthal
Ian A Taylor
Ian A
Taylor
Structure of a spumaretrovirus gag central domain reveals an ancient retroviral capsid
The Francis Crick Institute
2020
Amino Acid Sequence
Animals
Blotting, Western
Capsid
Capsid Proteins
Cell Line
Gene Products, gag
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Conformation
Real-Time Polymerase Chain Reaction
Spumavirus
Virus Assembly
Taylor, I FC001178
Stoye FC001162
Rosenthal FC001143
Taylor, W FC001179
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
2020-07-01 11:41:35
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Structure_of_a_spumaretrovirus_gag_central_domain_reveals_an_ancient_retroviral_capsid/12588962
The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.