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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7xn6 | ||||||
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タイトル | Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization | ||||||
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![]() | TOXIN / type III secretion system / Chromobacterium violaceum / caspase-3 / new PTM / programmed cell deathA / DP-ribosylation / ADPR-deacylization | ||||||
機能・相同性 | ![]() 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 / positive regulation of cyclic-nucleotide phosphodiesterase activity / Glycogen breakdown (glycogenolysis) / 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 / autophagosome membrane docking / mitochondrion-endoplasmic reticulum membrane tethering / 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 / negative regulation of B cell proliferation / pyroptotic inflammatory response / 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 / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / protein maturation / negative regulation of cell cycle / catalytic complex / DARPP-32 events / detection of calcium ion / response to X-ray / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / Caspase-mediated cleavage of cytoskeletal proteins / calcium channel inhibitor activity / RHO GTPases activate IQGAPs / cellular response to interferon-beta / regulation of macroautophagy / response to amino acid / cell fate commitment / 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 | ![]() ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.45 Å | ||||||
![]() | Zhang, K. / Peng, T. / Tao, X.Y. / Tian, M. / Li, Y.X. / Wang, Z. / Ma, S.F. / Hu, S.F. / Pan, X. / Xue, J. ...Zhang, K. / Peng, T. / Tao, X.Y. / Tian, M. / Li, Y.X. / Wang, Z. / Ma, S.F. / Hu, S.F. / Pan, X. / Xue, J. / Luo, J.W. / Wu, Q.L. / Fu, Y. / Li, S. | ||||||
資金援助 | 1件
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![]() | ![]() 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. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 163.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 127.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 40.6 KB | 表示 | |
CIF形式データ | ![]() | 56.7 KB | 表示 | |
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 | ![]() 33312MC ![]() 7xn4C ![]() 7xn5C M: このデータのモデリングに利用したマップデータ 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
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 31651.938 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | | 分子量: 52985.516 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: copC, CV_2038 / 発現宿主: ![]() 参照: UniProt: Q7NWF2, Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases #3: タンパク質 | | 分子量: 16852.545 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: 化合物 | ChemComp-APR / | #5: 化合物 | ChemComp-NCA / | 研究の焦点であるリガンドがあるか | N | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.45 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 82876 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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