title: Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.
abstract: Vaccinia virus (VACV) uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC), a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs). Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD) motif, which is conserved in the kinesin-1-binding sequence (KBS) of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.
authors.affiliation: Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Gareth W
authors.initials: GW
authors.lastname: Morgan
authors.forename: Michael
authors.initials: M
authors.lastname: Hollinshead
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ferguson
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Murphy
authors.forename: David C J
authors.initials: DC
authors.lastname: Carpentier
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D014616:Vaccinia virus / Q000472:pathogenicity / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000472:pathogenicity / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D014764:Viral Proteins; D016547:Kinesins