Acidic nuclear phosphoprotein 32 family member A / Polymerase basic protein 2 / RNA-directed RNA polymerase catalytic subunit / Polymerase acidic protein 類似検索 - 構成要素
生物種
Influenza C virus (C/Johannesburg/1/66) (インフルエンザウイルス) / Gallus gallus (ニワトリ) / Synthetic construct (人工物) / Influenza C virus (strain C/Johannesburg/1/1966) (インフルエンザウイルス)
ジャーナル: Nature / 年: 2020 タイトル: Host ANP32A mediates the assembly of the influenza virus replicase. 著者: Loïc Carrique / Haitian Fan / Alexander P Walker / Jeremy R Keown / Jane Sharps / Ecco Staller / Wendy S Barclay / Ervin Fodor / Jonathan M Grimes / 要旨: Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by ...Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.
フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / デジタル化 - 画像ごとのフレーム数: 1-44 / 撮影したグリッド数: 1 / 実像数: 3678 / 平均露光時間: 11.0 sec. / 平均電子線量: 38.8 e/Å2 詳細: Single specimen tilt of 30 degrees for around two third of the images