Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal.
Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.
Charles Sturt University, School of Animal and Veterinary Sciences, Boorooma St, Wagga Wagga, New South Wales 2678, Australia.
Edward I
EI
Patterson
Andrew K
AK
Dombrovski
Crystall M D
CM
Swarbrick
Shane R
SR
Raidal
Jade K
JK
Forwood
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D018173:Circoviridae Infections / Q000821:virology*; D017925:Circovirus / Q000737:chemistry / Q000502:physiology*; D018360:Crystallography, X-Ray; D054884:Host-Pathogen Interactions; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D028901:alpha Karyopherins / Q000737:chemistry / Q000378:metabolism*
D036022:Capsid Proteins; D019913:Nuclear Localization Signals; D028901:alpha Karyopherins
Beak and feather disease virus; Circovirus; Importin alpha; Nuclear localization signal