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基本情報
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タイトル | SARS-CoV-2 polyprotein substrate regulates the stepwise Mpro cleavage reaction | |||||||||
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![]() | SARS COV-2 Main protease (Mpro) in complex with the polyprotein substrate / VIRAL PROTEIN | |||||||||
機能・相同性 | ![]() viral genome replication / methyltransferase activity / protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / 付加脱離酵素(リアーゼ); P-Oリアーゼ類; - / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins ...viral genome replication / methyltransferase activity / protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / 付加脱離酵素(リアーゼ); P-Oリアーゼ類; - / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / TRAF3-dependent IRF activation pathway / Replication of the SARS-CoV-2 genome / snRNP Assembly / double membrane vesicle viral factory outer membrane / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エキソリボヌクレアーゼ / 5'-3' DNA helicase activity / SARS coronavirus main proteinase / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / host cell endosome / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / omega peptidase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / host cell Golgi apparatus / methyltransferase cap1 / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / endonuclease activity / methylation / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ / single-stranded RNA binding / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / viral protein processing / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / copper ion binding / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / lipid binding / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.49 Å | |||||||||
![]() | Narwal M / Edwards T / Armache JP / Murakami KS | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: SARS-CoV-2 polyprotein substrate regulates the stepwise M cleavage reaction. 著者: Manju Narwal / Jean-Paul Armache / Thomas J Edwards / Katsuhiko S Murakami / ![]() 要旨: The processing of the Coronavirus polyproteins pp1a and pp1ab by the main protease M to produce mature proteins is a crucial event in virus replication and a promising target for antiviral drug ...The processing of the Coronavirus polyproteins pp1a and pp1ab by the main protease M to produce mature proteins is a crucial event in virus replication and a promising target for antiviral drug development. M cleaves polyproteins in a defined order, but how M and/or the polyproteins determine the order of cleavage remains enigmatic due to a lack of structural information about polyprotein-bound M. Here, we present the cryo-EM structures of SARS-CoV-2 M in an apo form and in complex with the nsp7-10 region of the pp1a polyprotein. The complex structure shows that M interacts with only the recognition site residues between nsp9 and nsp10, without any association with the rest of the polyprotein. Comparison between the apo form and polyprotein-bound structures of M highlights the flexible nature of the active site region of M, which allows it to accommodate ten recognition sites found in the polyprotein. These observations suggest that the role of M in selecting a preferred cleavage site is limited and underscores the roles of the structure, conformation, and/or dynamics of the polyproteins in determining the sequence of polyprotein cleavage by M. | |||||||||
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 116 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 15.2 KB 15.2 KB | 表示 表示 | ![]() |
画像 | ![]() | 33.6 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
その他 | ![]() ![]() | 116 MB 116 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8eirMC ![]() 8ekeC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
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ボクセルのサイズ | X=Y=Z: 0.855 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #1
ファイル | emd_28162_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_28162_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : SARS COV-2 Mpro in complex with polyprotein substrate
全体 | 名称: SARS COV-2 Mpro in complex with polyprotein substrate |
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要素 |
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-超分子 #1: SARS COV-2 Mpro in complex with polyprotein substrate
超分子 | 名称: SARS COV-2 Mpro in complex with polyprotein substrate タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: 3C-like proteinase nsp5
分子 | 名称: 3C-like proteinase nsp5 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO / EC番号: SARS coronavirus main proteinase |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 33.79348 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SGFRKMAFPS GKVEGCMVQV TCGTTTLNGL WLDDVVYCPR HVICTSEDML NPNYEDLLIR KSNHNFLVQA GNVQLRVIGH SMQNCVLKL KVDTANPKTP KYKFVRIQPG QTFSVLACYN GSPSGVYQCA MRPNFTIKGS FLNGSAGSVG FNIDYDCVSF C YMHHMELP ...文字列: SGFRKMAFPS GKVEGCMVQV TCGTTTLNGL WLDDVVYCPR HVICTSEDML NPNYEDLLIR KSNHNFLVQA GNVQLRVIGH SMQNCVLKL KVDTANPKTP KYKFVRIQPG QTFSVLACYN GSPSGVYQCA MRPNFTIKGS FLNGSAGSVG FNIDYDCVSF C YMHHMELP TGVHAGTDLE GNFYGPFVDR QTAQAAGTDT TITVNVLAWL YAAVINGDRW FLNRFTTTLN DFNLVAMKYN YE PLTQDHV DILGPLSAQT GIAVLDMCAS LKELLQNGMN GRTILGSALL EDEFTPFDVV RQCSGVTFQ UniProtKB: Replicase polyprotein 1ab |
-分子 #2: nsp7-nsp10 of Replicase polyprotein 1a
分子 | 名称: nsp7-nsp10 of Replicase polyprotein 1a / タイプ: protein_or_peptide / ID: 2 詳細: nsp9/10 cleavage site is the portion visible in the map コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 58.29175 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SKMSDVKCTS VVLLSVLQQL RVESSSKLWA QCVQLHNDIL LAKDTTEAFE KMVSLLSVLL SMQGAVDINK LCEEMLDNRA TLQAIASEF SSLPSYAAFA TAQEAYEQAV ANGDSEVVLK KLKKSLNVAK SEFDRDAAMQ RKLEKMADQA MTQMYKQARS E DKRAKVTS ...文字列: SKMSDVKCTS VVLLSVLQQL RVESSSKLWA QCVQLHNDIL LAKDTTEAFE KMVSLLSVLL SMQGAVDINK LCEEMLDNRA TLQAIASEF SSLPSYAAFA TAQEAYEQAV ANGDSEVVLK KLKKSLNVAK SEFDRDAAMQ RKLEKMADQA MTQMYKQARS E DKRAKVTS AMQTMLFTML RKLDNDALNN IINNARDGCV PLNIIPLTTA AKLMVVIPDY NTYKNTCDGT TFTYASALWE IQ QVVDADS KIVQLSEISM DNSPNLAWPL IVTALRANSA VKLQNNELSP VALRQMSCAA GTTQTACTDD NALAYYNTTK GGR FVLALL SDLQDLKWAR FPKSDGTGTI YTELEPPCRF VTDTPKGPKV KYLYFIKGLN NLNRGMVLGS LAATVRLQAG NATE VPANS TVLSFCAFAV DAAKAYKDYL ASGGQPITNC VKMLCTHTGT GQAITVTPEA NMDQESFGGA SCCLYCRCHI DHPNP KGFC DLKGKYVQIP TTCANDPVGF TLKNTVCTVC GMWKGYGCSC DQLREPMLQ UniProtKB: Replicase polyprotein 1a |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1 mg/mL |
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緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: OTHER / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.49 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 244544 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |