National Institutes of Health/National Cancer Institute (NIH/NCI)
U54-CA193419
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
P01-CA092584
米国
American Cancer Society
IRG-15-173-21
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32-GM008382
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2020 タイトル: Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation. 著者: Ryan Abdella / Megha Aggarwal / Takashi Okura / Robert A Lamb / Yuan He / 要旨: 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 ...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 ∼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-Å resolution using cryoelectron microscopy, as well as the oligomerization domain (OD) of P at 1.4-Å 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.
名称: Phosphoprotein / タイプ: protein_or_peptide / ID: 2 詳細: Chain F belongs to the same peptide as one of B, C, D or E, but the density is not well resolved enough to determine which chain it should associate with. コピー数: 5 / 光学異性体: LEVO