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Negative-Strand RNA Virus L Proteins: One Machine, Many Activities
Kalyan Das, Eddy Arnold Cell Volume 162, Issue 2, Pages (July 2015) DOI: /j.cell Copyright © 2015 Elsevier Inc. Terms and Conditions
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Figure 1 L Proteins of Segmented and Non-segmented Negative-Sense Single-Strand RNA Viruses (A) The structure of La Crosse orthobunyavirus (LACV) L protein (PDB ID 5AMQ), representing the segmented NSV viral single chain RdRp. The RdRp core has a right hand-like structure with fingers (blue), palm (salmon), and thumb (green) domains. The N-terminal 195 residues form the endonuclease domain (cyan), and 518 C-terminal residues that include the cap-binding domain are missing in the structure. The cap-binding domain (orange) of influenza RdRp is positioned based on superposition of RdRp cores of the two structures. (B) The structure of vesicular stomatitis virus (VSV) L protein (PDB ID: 5A22), representing the non-segmented NSV viral RdRp. The positioning of the polyribonucleotidyl transferase (PRNTase) over the polymerase core suggests that the L protein would undergo significant conformational changes for carrying out replication and transcription. (C) Cap-snatching mechanism that segmented NSVs including LACV execute for transcription of viral mRNAs. In this process, the cap-binding domain binds the pre-formed m7Gppp cap of a host mRNA, the endonuclease domain cleaves the mRNA after 10–13 nucleotides by a two Mg2+ ion-dependent catalytic nuclease reaction, and the viral mRNA synthesis complementing a vRNA segment starts from the 3′-end of the cleaved mRNA piece. (D) An unconventional PRNTase-mediated capping mechanism employed by non-segmented NSVs including VSV. In this process, the catalytic H1227 in the PRNTase domain of VSV L protein forms a covalent histidyl-p-RNA intermediate, and a nucleophilic attack by a β-oxygen of GDP breaks the phosphoamide bond and adds a Gppp cap structure at the 5′-end of the nascent RNA. The methyltransferase (MTase) domain methylates the ribose 2′-O and N7 positions to complete the m7Gppp capping process. Cell , DOI: ( /j.cell ) Copyright © 2015 Elsevier Inc. Terms and Conditions
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