title: Assembly of the Ebola Virus Nucleoprotein from a Chaperoned VP35 Complex.
abstract: Ebolavirus NP oligomerizes into helical filaments found at the core of the virion, encapsidates the viral RNA genome, and serves as a scaffold for additional viral proteins within the viral nucleocapsid. We identified a portion of the phosphoprotein homolog VP35 that binds with high affinity to nascent NP and regulates NP assembly and viral genome binding. Removal of the VP35 peptide leads to NP self-assembly via its N-terminal oligomerization arm. NP oligomerization likely causes a conformational change between the NP N- and C-terminal domains, facilitating RNA binding. These functional data are complemented by crystal structures of the NP°-VP35 complex at 2.4 Å resolution. The interactions between NP and VP35 illuminated by these structures are conserved among filoviruses and provide key targets for therapeutic intervention.
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Kirchdoerfer
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dafna M
authors.initials: DM
authors.lastname: Abelson
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Core Microscopy Facility, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Wood
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: erica@scripps.edu.
authors.forename: Erica Ollmann
authors.initials: EO
authors.lastname: Saphire
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins; C084818:nucleoprotein VP35, Ebola virus; D012313:RNA