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Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid

Ball, NJ; Nicastro, G; Dutta, M; Pollard, DJ; Goldstone, DC; Sanz-Ramos, M; Ramos, A; ... Taylor, IA; + view all (2016) Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid. PLOS Pathogens , 12 (11) , Article e1005981. 10.1371/journal.ppat.1005981. Green open access

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Abstract

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.

Type: Article
Title: Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1005981
Publisher version: http://dx.doi.org/10.1371/journal.ppat.1005981
Language: English
Additional information: Copyright © 2016 Ball et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1531022
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