The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription

PLoS Pathogens

Julien Lescar¹  Saïd Jamal¹  Antoine Frangeul¹  Bruno Coutard¹  Benjamin Morin¹  François Ferron¹  Michaela Lelke²  Bruno Canard²  Romy Kerber²  Clemens Vonrhein³  Stephan Günther³  Gérard Bricogne⁴  Cécile Baronti⁵  Xavier de Lamballerie⁵  Rémi Charrel⁵ 

[1] Architecture et Fonction des Macromolécules Biologiques, CNRS and Universités d'Aix-Marseille I et II, UMR 6098, ESIL Case 925, Marseille, France;Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany;Global Phasing Ltd., Cambridge, United Kingdom;School of Biological Sciences, Nanyang Technological University, Singapore, Singapore;Unité des Virus Emergents UMR190, Université de la Méditerranée & Institut de Recherche pour le Développement, Marseille, France

关键词: Sequence motif analysis;    Crystal structure;    RNA synthesis;    Arenaviruses;    Bunyaviruses;    Messenger RNA;    Influenza viruses;    Viral structure;   

DOI  :  10.1371/journal.ppat.1001038

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY