title: Structural insights into the assembly and regulation of distinct viral capsid complexes.
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.
authors.affiliation: School of Animal and Veterinary Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2678, Australia.|Graham Centre for Agricultural Innovation, NSW Department of Primary Industries and Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2678, Australia.
authors.forename: Subir
authors.identifier: 0000-0002-2685-8377
authors.initials: S
authors.lastname: Sarker
authors.affiliation: Centro Nacional de Microbiología/ISCIII, Majadahonda, Madrid 28220, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Terrón
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales 2678, Australia.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Khandokar
authors.affiliation: Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Aragão
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Joshua M
authors.identifier: 0000-0002-8014-8552
authors.initials: JM
authors.lastname: Hardy
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Mazdak
authors.initials: M
authors.lastname: Radjainia
authors.affiliation: Física de la Materia Condensada, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez-Zaragoza
authors.affiliation: Física de la Materia Condensada, Universidad Autónoma de Madrid, 28049 Madrid, Spain.|Insituto de Física de la Materia Condensada (IFIMAC), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: de Pablo
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Fasséli
authors.initials: F
authors.lastname: Coulibaly
authors.affiliation: Centro Nacional de Microbiología/ISCIII, Majadahonda, Madrid 28220, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Luque
authors.affiliation: School of Animal and Veterinary Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2678, Australia.|Graham Centre for Agricultural Innovation, NSW Department of Primary Industries and Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2678, Australia.
authors.forename: Shane R
authors.identifier: 0000-0001-7917-8976
authors.initials: SR
authors.lastname: Raidal
authors.affiliation: Graham Centre for Agricultural Innovation, NSW Department of Primary Industries and Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2678, Australia.|School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales 2678, Australia.
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D046911:Macromolecular Substances; D011487:Protein Conformation; D000072417:Protein Domains; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D046911:Macromolecular Substances; D001120:Arginine