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Publication Abstract from PubMed

Paramyxoviruses are enveloped, nonsegmented, negative-strand RNA viruses that cause a wide spectrum of human and animal diseases. The viral genome, packaged by the nucleoprotein (N), serves as a template for the polymerase complex, composed of the large protein (L) and the homo-tetrameric phosphoprotein (P). The approximately 250-kDa L possesses all enzymatic activities necessary for its function but requires P in vivo. Structural information is available for individual P domains from different paramyxoviruses, but how P interacts with L and how that affects the activity of L is largely unknown due to the lack of high-resolution structures of this complex in this viral family. In this study we determined the structure of the L-P complex from parainfluenza virus 5 (PIV5) at 4.3-A resolution using cryoelectron microscopy, as well as the oligomerization domain (OD) of P at 1.4-A resolution using X-ray crystallography. P-OD associates with the RNA-dependent RNA polymerase domain of L and protrudes away from it, while the X domain of one chain of P is bound near the L nucleotide entry site. The methyltransferase (MTase) domain and the C-terminal domain (CTD) of L adopt a unique conformation, positioning the MTase active site immediately above the poly-ribonucleotidyltransferase domain and near the likely exit site for the product RNA 5' end. Our study reveals a potential mechanism that mononegavirus polymerases may employ to switch between transcription and genome replication. This knowledge will assist in the design and development of antivirals against paramyxoviruses.

Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation.,Abdella R, Aggarwal M, Okura T, Lamb RA, He Y Proc Natl Acad Sci U S A. 2020 Feb 19. pii: 1919837117. doi:, 10.1073/pnas.1919837117. PMID:32075920^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.