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

PLoS Pathogens

Peter B. Rosenthal¹  William R. Taylor²  Erik Müllers³  Nicole Stanke³  Dirk Lindemann³  Kristin Stirnnagel³  David C. Goldstone⁴  Andres Ramos⁴  Dominic J. Pollard⁴  Giuseppe Nicastro⁴  Neil J. Ball⁴  Jonathan P. Stoye⁵  Marta Sanz-Ramos⁵  Moumita Dutta⁶  Ian A. Taylor⁶ 

[1] Computational Cell and Molecular Biology Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom;Faculty of Medicine, Imperial College London, London, United Kingdom;Institute of Virology, Technische Universität Dresden, Dresden, DE;Macromolecular Structure Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom;Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom;Structural Biology of Cells and Viruses, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom

关键词: Protein structure;    Sequence motif analysis;    HIV-1;    Sedimentation;    Viral packaging;    Protein structure comparison;    Viral core;    Viral structure;   

DOI  :  10.1371/journal.ppat.1005981

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY