+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33312 | |||||||||
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タイトル | Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | type III secretion system / Chromobacterium violaceum / caspase-3 / new PTM / programmed cell deathA / DP-ribosylation / ADPR-deacylization / TOXIN | |||||||||
機能・相同性 | 機能・相同性情報 Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases / ADP-riboxanase activity / symbiont-mediated perturbation of host programmed cell death / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response ...Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases / ADP-riboxanase activity / symbiont-mediated perturbation of host programmed cell death / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / NADE modulates death signalling / luteolysis / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / death-inducing signaling complex / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to staurosporine / Apoptosis induced DNA fragmentation / cysteine-type endopeptidase activity involved in execution phase of apoptosis / Caspase activation via Dependence Receptors in the absence of ligand / Apoptotic cleavage of cell adhesion proteins / death receptor binding / SMAC, XIAP-regulated apoptotic response / Activation of caspases through apoptosome-mediated cleavage / axonal fasciculation / Signaling by Hippo / cysteine-type endopeptidase activity involved in apoptotic process / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / Calmodulin induced events / fibroblast apoptotic process / execution phase of apoptosis / Reduction of cytosolic Ca++ levels / negative regulation of cytokine production / epithelial cell apoptotic process / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / platelet formation / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / Other interleukin signaling / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / positive regulation of amyloid-beta formation / Activation of RAC1 downstream of NMDARs / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Apoptotic cleavage of cellular proteins / Unblocking of NMDA receptors, glutamate binding and activation / pyroptotic inflammatory response / negative regulation of B cell proliferation / Phase 0 - rapid depolarisation / T cell homeostasis / protein phosphatase activator activity / negative regulation of activated T cell proliferation / RHO GTPases activate PAKs / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / B cell homeostasis / Long-term potentiation / neurotrophin TRK receptor signaling pathway / Uptake and function of anthrax toxins / protein maturation / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / negative regulation of cell cycle / catalytic complex / DARPP-32 events / response to X-ray / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / RHO GTPases activate IQGAPs / Caspase-mediated cleavage of cytoskeletal proteins / calcium channel inhibitor activity / cellular response to interferon-beta / response to amino acid / cell fate commitment / regulation of macroautophagy / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / response to tumor necrosis factor / Pyroptosis / Protein methylation 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Chromobacterium violaceum (バクテリア) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.45 Å | |||||||||
データ登録者 | Zhang K / Peng T / Tao XY / Tian M / Li YX / Wang Z / Ma SF / Hu SF / Pan X / Xue J ...Zhang K / Peng T / Tao XY / Tian M / Li YX / Wang Z / Ma SF / Hu SF / Pan X / Xue J / Luo JW / Wu QL / Fu Y / Li S | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Mol Cell / 年: 2022 タイトル: Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin. 著者: Kuo Zhang / Ting Peng / Xinyuan Tao / Miao Tian / Yanxin Li / Zhao Wang / Shuaifei Ma / Shufan Hu / Xing Pan / Juan Xue / Jiwei Luo / Qiulan Wu / Yang Fu / Shan Li / 要旨: Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal ...Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR deacylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33312.map.gz | 167.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33312-v30.xml emd-33312.xml | 17 KB 17 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_33312.png | 179.5 KB | ||
Filedesc metadata | emd-33312.cif.gz | 6.3 KB | ||
その他 | emd_33312_half_map_1.map.gz emd_33312_half_map_2.map.gz | 165.2 MB 165.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33312 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33312 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33312_validation.pdf.gz | 918 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33312_full_validation.pdf.gz | 917.6 KB | 表示 | |
XML形式データ | emd_33312_validation.xml.gz | 15.4 KB | 表示 | |
CIF形式データ | emd_33312_validation.cif.gz | 18.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33312 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33312 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_33312.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.842 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: #2
ファイル | emd_33312_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: #1
ファイル | emd_33312_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 |
-試料の構成要素
-全体 : Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization
全体 | 名称: Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization |
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要素 |
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-超分子 #1: Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization
超分子 | 名称: Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Caspase-3
分子 | 名称: Caspase-3 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO / EC番号: caspase-3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 32.175195 KDa |
組換発現 | 生物種: Bacteria Latreille et al. 1825 (昆虫) |
配列 | 文字列: MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKN DLTREEIVEL MRDVSKEDHS KRSSFVCVLL SHGEEGIIFG TNGPVDLKKI TNFFRGDRCR SLTGKPKLFI I QACRGTEL ...文字列: MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKN DLTREEIVEL MRDVSKEDHS KRSSFVCVLL SHGEEGIIFG TNGPVDLKKI TNFFRGDRCR SLTGKPKLFI I QACRGTEL DCGIETDSGV DDDMACHKIP VEADFLYAYS TAPGYYSW(A1LTQ)N SKDGSWFIQS LCAMLKQYAD KLEFMH ILT RVNRKVATEF ESFSFDATFH AKKQIPCIVS MLTKELYFYH UniProtKB: Caspase-3 |
-分子 #2: Arginine ADP-riboxanase CopC
分子 | 名称: Arginine ADP-riboxanase CopC / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO EC番号: Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases |
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由来(天然) | 生物種: Chromobacterium violaceum (バクテリア) |
分子量 | 理論値: 52.985516 KDa |
組換発現 | 生物種: Bacteria Latreille et al. 1825 (昆虫) |
配列 | 文字列: MRVENHSPSL SKLNPPEAGS GDPTAIGRRL SGIRRAPLPH VSAGSDGEAA AAGKIGAFLR KAVAAQSYGL MFANGKLFEA TGDALEKRG QYGFSALQRL DGLSRRNLAA VEARLGALDS AERGLKERIM TGAWHFRHQS NAALDDGKTA AIASNHLLAR E SRSSGGNT ...文字列: MRVENHSPSL SKLNPPEAGS GDPTAIGRRL SGIRRAPLPH VSAGSDGEAA AAGKIGAFLR KAVAAQSYGL MFANGKLFEA TGDALEKRG QYGFSALQRL DGLSRRNLAA VEARLGALDS AERGLKERIM TGAWHFRHQS NAALDDGKTA AIASNHLLAR E SRSSGGNT FAGDKALLSN HDFVFFGVEF SGRGKQDKPL NHKHSTMDFG ANAYVVPDTL PACRHGYLTL TDHFFNRVPG GR EAEHQDF VGSFPQMGAE TGRWIHEGKY RQNAPIFNYR DMKAAVALHL IEFLRDSKDA AFKAYVFDQA MQSGQALDRV LNS VFQAEF HIPRLMATTD YAKHPLRPML LKEAVDSVNL PALSGLVSSK GDAVTAMWHA IDKGKDAVAA HLLGNWRFEA GDFA SAPPG FYHELNYALS EHGASVYILD QFLSRGWAAV NAPFEHVNSG ETMLDNAVKY GNREMAAALI KHGADRNLLS EWNGG KLDA LLA UniProtKB: Arginine ADP-riboxanase CopC |
-分子 #3: Calmodulin-1
分子 | 名称: Calmodulin-1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 16.852545 KDa |
組換発現 | 生物種: Bacteria Latreille et al. 1825 (昆虫) |
配列 | 文字列: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK UniProtKB: Calmodulin-1 |
-分子 #4: NICOTINAMIDE
分子 | 名称: NICOTINAMIDE / タイプ: ligand / ID: 4 / コピー数: 1 / 式: NCA |
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分子量 | 理論値: 122.125 Da |
Chemical component information | ChemComp-NCA: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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 K2 SUMMIT (4k x 4k) 平均電子線量: 40.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.45 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 82876 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |