title: The N-terminal domain of the arenavirus L protein is an RNA endonuclease essential in mRNA transcription.
abstract: Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a 'cap-snatching' mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS and Universités d'Aix-Marseille I et II, UMR 6098, ESIL Case 925, Marseille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Morin
authors.forename: Bruno
authors.initials: B
authors.lastname: Coutard
authors.forename: Michaela
authors.initials: M
authors.lastname: Lelke
authors.forename: François
authors.initials: F
authors.lastname: Ferron
authors.forename: Romy
authors.initials: R
authors.lastname: Kerber
authors.forename: Saïd
authors.initials: S
authors.lastname: Jamal
authors.forename: Antoine
authors.initials: A
authors.lastname: Frangeul
authors.forename: Cécile
authors.initials: C
authors.lastname: Baronti
authors.forename: Rémi
authors.initials: R
authors.lastname: Charrel
authors.forename: Xavier
authors.initials: X
authors.lastname: de Lamballerie
authors.forename: Clemens
authors.initials: C
authors.lastname: Vonrhein
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
authors.forename: Gérard
authors.initials: G
authors.lastname: Bricogne
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
mesh_terms: D002043:Bunyaviridae / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D004720:Endonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D016296:Mutagenesis; D009975:Orthomyxoviridae / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D004720:Endonucleases; D004722:Endoribonucleases