Structural insights into the assembly and regulation of distinct viral capsid complexes

Subir Sarker, María C. Terrón, Yogesh Khandokar, David Aragao, Joshua M. Hardy, Mazdak Radjainia, Manuel Jiménez-Zaragoza, Pedro J. De Pablo, Fasseli Coulibaly, Daniel Luque, Shane R. Raidal, Jade K. Forwood

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The assembly and regulation of viral capsid proteins into highly ordered macromolecular complexes is essential for viral replication. Here, we utilize crystal structures of the capsid protein from the smallest and simplest known viruses capable of autonomously replicating in animal cells, circoviruses, to establish structural and mechanistic insights into capsid morphogenesis and regulation. The beak and feather disease virus, like many circoviruses, encode only two genes: a capsid protein and a replication initiation protein. The capsid protein forms distinct macromolecular assemblies during replication and here we elucidate these structures at high resolution, showing that these complexes reverse the exposure of the N-terminal arginine rich domain responsible for DNA binding and nuclear localization. We show that assembly of these complexes is regulated by single-stranded DNA (ssDNA), and provide a structural basis of capsid assembly around single-stranded DNA, highlighting novel binding interfaces distinct from the highly positively charged N-terminal ARM domain.

Original languageEnglish
Article number13014
Number of pages7
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 4 Oct 2016

Keywords

  • microbiology
  • pathogens
  • structural biology
  • virus structures

Cite this

Sarker, Subir ; Terrón, María C. ; Khandokar, Yogesh ; Aragao, David ; Hardy, Joshua M. ; Radjainia, Mazdak ; Jiménez-Zaragoza, Manuel ; De Pablo, Pedro J. ; Coulibaly, Fasseli ; Luque, Daniel ; Raidal, Shane R. ; Forwood, Jade K. / Structural insights into the assembly and regulation of distinct viral capsid complexes. In: Nature Communications. 2016 ; Vol. 7.
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abstract = "The assembly and regulation of viral capsid proteins into highly ordered macromolecular complexes is essential for viral replication. Here, we utilize crystal structures of the capsid protein from the smallest and simplest known viruses capable of autonomously replicating in animal cells, circoviruses, to establish structural and mechanistic insights into capsid morphogenesis and regulation. The beak and feather disease virus, like many circoviruses, encode only two genes: a capsid protein and a replication initiation protein. The capsid protein forms distinct macromolecular assemblies during replication and here we elucidate these structures at high resolution, showing that these complexes reverse the exposure of the N-terminal arginine rich domain responsible for DNA binding and nuclear localization. We show that assembly of these complexes is regulated by single-stranded DNA (ssDNA), and provide a structural basis of capsid assembly around single-stranded DNA, highlighting novel binding interfaces distinct from the highly positively charged N-terminal ARM domain.",
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year = "2016",
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Sarker, S, Terrón, MC, Khandokar, Y, Aragao, D, Hardy, JM, Radjainia, M, Jiménez-Zaragoza, M, De Pablo, PJ, Coulibaly, F, Luque, D, Raidal, SR & Forwood, JK 2016, 'Structural insights into the assembly and regulation of distinct viral capsid complexes' Nature Communications, vol. 7, 13014. https://doi.org/10.1038/ncomms13014

Structural insights into the assembly and regulation of distinct viral capsid complexes. / Sarker, Subir; Terrón, María C.; Khandokar, Yogesh; Aragao, David; Hardy, Joshua M.; Radjainia, Mazdak; Jiménez-Zaragoza, Manuel; De Pablo, Pedro J.; Coulibaly, Fasseli; Luque, Daniel; Raidal, Shane R.; Forwood, Jade K.

In: Nature Communications, Vol. 7, 13014, 04.10.2016.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hardy, Joshua M.

AU - Radjainia, Mazdak

AU - Jiménez-Zaragoza, Manuel

AU - De Pablo, Pedro J.

AU - Coulibaly, Fasseli

AU - Luque, Daniel

AU - Raidal, Shane R.

AU - Forwood, Jade K.

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