Structural insights into the assembly and regulation of distinct viral capsid complexes
journal contributionposted on 09.11.2020, 00:25 authored by S Sarker, MC Terron, Y Khandokar, D Aragao, JM Hardy, M Radjainia, M Jimenez-Zaragoza, PJ de Pablo, F Coulibaly, D Luque, SR Raidal, JK Forwood
© The Author(s) 2016. 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.
J.K.F. and F.C. are funded by Future Fellowships of the Australian Research Council. We thank the Clive and Vera Ramaciotti Centre for Cryo Electron Microscopy and the Australian Synchrotron for their technical support.
Australian Research Council
PublisherNature Publishing Group
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Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsPORCINE CIRCOVIRUSVIRUSREPLICATIONSUITEBEAKDNAAnimalsVirionCapsidMacromolecular SubstancesArginineCapsid ProteinsDNA, Single-StrandedDNA, ViralCrystallography, X-RayVirus ReplicationVirus AssemblyDNA ReplicationProtein ConformationProtein Domains