登録情報 データベース : EMDB / ID : EMD-34402 ダウンロードとリンクタイトル Cryo-EM structure of the the NS5-NS3 RNA-elongation complex マップデータ 詳細 試料複合体 : NS5-NS3 RNA-elongation complex複合体 : NS5タンパク質・ペプチド : Genome polyprotein複合体 : NS3タンパク質・ペプチド : Genome polyprotein複合体 : RNA リボ核酸RNA : RNA リボ核酸リガンド : MANGANESE (II) IONリガンド : ZINC IONリガンド : S-ADENOSYL-L-HOMOCYSTEINE S-アデノシル-L-ホモシステインリガンド : CYTIDINE-5'-DIPHOSPHATE 詳細 キーワード viral genome replication / VIRAL PROTEIN (ウイルスタンパク質)機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / : / カプシド / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity ... symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / : / カプシド / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / induction by virus of host autophagy / viral RNA genome replication / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / エンベロープ (ウイルス) / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / virion attachment to host cell / virion membrane / structural molecule activity / タンパク質分解 / extracellular region / ATP binding / 生体膜 / metal ion binding 類似検索 - 分子機能 : / Flavivirus envelope glycoprotein E, stem/anchor domain / Flavivirus capsid protein C superfamily / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus non-structural protein NS2B / : / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A ... : / Flavivirus envelope glycoprotein E, stem/anchor domain / Flavivirus capsid protein C superfamily / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus non-structural protein NS2B / : / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / Envelope glycoprotein M, flavivirus / Flavivirus envelope glycoprotein M / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M superfamily, flavivirus / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / helicase superfamily c-terminal domain / Immunoglobulin E-set / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性生物種 Dengue virus (デング熱ウイルス) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.8 Å 詳細 データ登録者Osawa T / Ehara H / Sekine S 資金援助 日本, 1件 詳細 詳細を隠すOrganization Grant number 国 Japan Society for the Promotion of Science (JSPS) 日本
引用ジャーナル : Mol Cell / 年 : 2023タイトル : Structures of dengue virus RNA replicase complexes.著者 : Takuo Osawa / Mari Aoki / Haruhiko Ehara / Shun-Ichi Sekine / 要旨 : Dengue is a mosquito-borne viral infection caused by dengue virus (DENV), a member of the flaviviruses. The DENV genome is a 5'-capped positive-sense RNA with a unique 5'-stem-loop structure (SLA), ... Dengue is a mosquito-borne viral infection caused by dengue virus (DENV), a member of the flaviviruses. The DENV genome is a 5'-capped positive-sense RNA with a unique 5'-stem-loop structure (SLA), which is essential for RNA replication and 5' capping. The virus-encoded proteins NS5 and NS3 are responsible for viral genome replication, but the structural basis by which they cooperatively conduct the required tasks has remained unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of SLA-bound NS5 (PC), NS3-bound PC (PC-NS3), and an RNA-elongating NS5-NS3 complex (EC). While SLA bridges the NS5 methyltransferase and RNA-dependent RNA polymerase domains in PC, the NS3 helicase domain displaces it in elongation complex (EC). The SLA- and NS3-binding sites overlap with that of human STAT2. These structures illuminate the key steps in DENV genome replication, namely, SLA-dependent replication initiation, processive RNA elongation, and 5' capping of the nascent genomic RNA, thereby providing foundations to combat flaviviruses. 履歴 登録 2022年9月27日 - ヘッダ(付随情報) 公開 2023年8月2日 - マップ公開 2023年8月2日 - 更新 2023年8月23日 - 現状 2023年8月23日 処理サイト : PDBj / 状態 : 公開
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