5j1n | pdb_00005j1n
Lassa virus L protein cap-snatching endonuclease. Bound to one manganese ion
Structural highlights
Function[Q6GWS6_9VIRU] RNA-dependent RNA polymerase which is responsible for replication and transcription of the viral RNA genome. During transcription, synthesizes 4 subgenomic RNAs, and assures their capping by a cap-snatching mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are heterogeneous and not polyadenylated. The replicase function is to direct synthesis of antigenomic and genomic RNA which are encapsidated and non capped. As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated. These processes may be regulated by proteins N and Z in a dose-dependent manner.[PIRNR:PIRNR000836] Publication Abstract from PubMedSegmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5' end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase. Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases.,Reguera J, Gerlach P, Rosenthal M, Gaudon S, Coscia F, Gunther S, Cusack S PLoS Pathog. 2016 Jun 15;12(6):e1005636. doi: 10.1371/journal.ppat.1005636., eCollection 2016 Jun. PMID:27304209[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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