title: Structure of the Hantavirus Nucleoprotein Provides Insights into the Mechanism of RNA Encapsidation.
abstract: Hantaviruses are etiological agents of life-threatening hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. The nucleoprotein (N) of hantavirus is essential for viral transcription and replication, thus representing an attractive target for therapeutic intervention. We have determined the crystal structure of hantavirus N to 3.2 Å resolution. The structure reveals a two-lobed, mostly α-helical structure that is distantly related to that of orthobunyavirus Ns. A basic RNA binding pocket is located at the intersection between the two lobes. We provide evidence that oligomerization is mediated by amino- and C-terminal arms that bind to the adjacent monomers. Based on these findings, we suggest a model for the oligomeric ribonucleoprotein (RNP) complex. Our structure provides mechanistic insights into RNA encapsidation in the genus Hantavirus and constitutes a template for drug discovery efforts aimed at combating hantavirus infections.
authors.affiliation: Crystallography, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: daniel.olal@mdc-berlin.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olal
authors.affiliation: Crystallography, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany; Biochemie, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany. Electronic address: oliver.daumke@mdc-berlin.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Daumke
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006476:Orthohantavirus / Q000502:physiology* / Q000648:ultrastructure; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry* / Q000648:ultrastructure; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000648:ultrastructure; D019065:Virus Assembly
chemical_list: D009698:Nucleoproteins; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins