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-Structure paper
タイトル | Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 117, Issue 9, Page 4931-4941, Year 2020 |
掲載日 | 2020年3月3日 |
著者 | Ryan Abdella / Megha Aggarwal / Takashi Okura / Robert A Lamb / Yuan He / |
PubMed 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. |
リンク | Proc Natl Acad Sci U S A / PubMed:32075920 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.4 - 4.63 Å |
構造データ | EMDB-21095, PDB-6v85: EMDB-21096, PDB-6v86: PDB-6vag: |
化合物 | ChemComp-ZN: ChemComp-GOL: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN / POLYMERASE / METHYLTRANSFERASE / POLY-RIBONUCLEOTIDYLTRANSFERASE / Paramyxovirus / Phosphoprotein / Oligomerization domain |