5chs | pdb_00005chs
N-terminal domain of the vesicular stomatitis virus L protein
Structural highlights
FunctionL_VSIVM Displays RNA-directed RNA polymerase, mRNA guanylyl transferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). Functions either as transcriptase or as replicase. The transcriptase synthesizes subsequently five subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular N protein concentration. In this mode, the polymerase replicates the whole viral genome without recognizing the transcriptional signals (By similarity). Publication Abstract from PubMedViruses have varied mechanisms to duplicate their genomes and produce viral specific mRNAs. Negative strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from the Rhabdoviridae, Paramyxoviridae and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8A resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, included segmented negative-strand RNA and dsRNA viruses. IMPORTANCE: Negative strand RNA viruses include a diverse set of viral families that infect animals and plants causing serious illness and economic impact. This group of viruses share a common set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a unique set of reactions to produce genomic- and subgenomic-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative strand RNA viruses. Structure and function of the N-terminal domain of the vesicular stomatitis virus RNA polymerase.,Qiu S, Ogino M, Luo M, Ogino T, Green TJ J Virol. 2015 Oct 28. pii: JVI.02317-15. PMID:26512087[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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