title: An all-atom model of the pore-like structure of hexameric VP40 from Ebola: structural insights into the monomer-hexamer transition.
abstract: The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of approximately 30 A. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to approximately 20 A and the construction of an all-atom model (residues 44-212) using the EM model at approximately 20 A and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer-hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore, may provide the basis for elucidating the biological function of VP40.
authors.affiliation: Target Structure-Based Drug Discovery Group, Developmental Therapeutics Program, SAIC, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Tam Luong
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
authors.forename: Ann R
authors.initials: AR
authors.lastname: Hermone
authors.forename: James C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Rekha G
authors.initials: RG
authors.lastname: Panchal
authors.forename: Connor
authors.initials: C
authors.lastname: McGrath
authors.forename: Dan W
authors.initials: DW
authors.lastname: Zaharevitz
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.forename: Rick
authors.initials: R
authors.lastname: Gussio
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D008854:Microscopy, Electron; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry*; D011487:Protein Conformation; D014758:Viral Core Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D009698:Nucleoproteins; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus