+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 4uf3 | ||||||
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タイトル | Deerpox virus DPV022 in complex with Bim BH3 | ||||||
要素 |
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キーワード | VIRAL PROTEIN / DPV022 / DEERPOX VIRUS / APOPTOSIS / BCL-2 / BIM BH3 | ||||||
機能・相同性 | 機能・相同性情報 BIM-BCL-xl complex / BIM-BCL-2 complex / regulation of developmental pigmentation / RUNX3 regulates BCL2L11 (BIM) transcription / positive regulation of mitochondrial membrane permeability involved in apoptotic process / developmental pigmentation / Activation of BIM and translocation to mitochondria / positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of fibroblast apoptotic process / apoptotic process involved in embryonic digit morphogenesis ...BIM-BCL-xl complex / BIM-BCL-2 complex / regulation of developmental pigmentation / RUNX3 regulates BCL2L11 (BIM) transcription / positive regulation of mitochondrial membrane permeability involved in apoptotic process / developmental pigmentation / Activation of BIM and translocation to mitochondria / positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of fibroblast apoptotic process / apoptotic process involved in embryonic digit morphogenesis / ear development / meiosis I / mammary gland development / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / positive regulation of T cell apoptotic process / tube formation / regulation of organ growth / cellular response to glucocorticoid stimulus / Bcl-2 family protein complex / myeloid cell homeostasis / FOXO-mediated transcription of cell death genes / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / NRAGE signals death through JNK / thymocyte apoptotic process / T cell homeostasis / odontogenesis of dentin-containing tooth / positive regulation of IRE1-mediated unfolded protein response / positive regulation of release of cytochrome c from mitochondria / B cell homeostasis / host cell mitochondrion / host cell membrane / endomembrane system / positive regulation of cell cycle / positive regulation of intrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / spleen development / FLT3 Signaling / response to endoplasmic reticulum stress / cell-matrix adhesion / post-embryonic development / thymus development / kidney development / positive regulation of protein-containing complex assembly / activation of cysteine-type endopeptidase activity involved in apoptotic process / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by BRAF and RAF1 fusions / positive regulation of neuron apoptotic process / spermatogenesis / microtubule binding / regulation of apoptotic process / in utero embryonic development / mitochondrial outer membrane / positive regulation of apoptotic process / apoptotic process / protein kinase binding / mitochondrion / membrane / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Deerpox virus Homo sapiens (ヒト) | ||||||
手法 | X線回折 / シンクロトロン / 単一同系置換・異常分散 / 解像度: 2.7 Å | ||||||
データ登録者 | Burton, D.R. / Kvansakul, M. | ||||||
引用 | ジャーナル: Acta Crystallogr D Biol Crystallogr / 年: 2015 タイトル: Structural basis of Deerpox virus-mediated inhibition of apoptosis. 著者: Denis R Burton / Sofia Caria / Bevan Marshall / Michele Barry / Marc Kvansakul / 要旨: Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use ...Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use of Bcl-2 proteins, to ensure their own survival. Here, it is reported that the Deerpox virus inhibitor of apoptosis, DPV022, only engages a highly restricted set of death-inducing Bcl-2 proteins, including Bim, Bax and Bak, with modest affinities. Structural analysis reveals that DPV022 adopts a Bcl-2 fold with a dimeric domain-swapped topology and binds pro-death Bcl-2 proteins via two conserved ligand-binding grooves found on opposite sides of the dimer. Structures of DPV022 bound to Bim, Bak and Bax BH3 domains reveal that a partial obstruction of the binding groove is likely to be responsible for the modest affinities of DPV022 for BH3 domains. These findings reveal that domain-swapped dimeric Bcl-2 folds are not unusual and may be found more widely in viruses. Furthermore, the modest affinities of DPV022 for pro-death Bcl-2 proteins suggest that two distinct classes of anti-apoptotic viral Bcl-2 proteins exist: those that are monomeric and tightly bind a range of death-inducing Bcl-2 proteins, and others such as DPV022 that are dimeric and only bind a very limited number of death-inducing Bcl-2 proteins with modest affinities. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 4uf3.cif.gz | 78.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb4uf3.ent.gz | 60.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 4uf3.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 4uf3_validation.pdf.gz | 310.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 4uf3_full_validation.pdf.gz | 311.9 KB | 表示 | |
XML形式データ | 4uf3_validation.xml.gz | 7.7 KB | 表示 | |
CIF形式データ | 4uf3_validation.cif.gz | 9.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/uf/4uf3 ftp://data.pdbj.org/pub/pdb/validation_reports/uf/4uf3 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 19633.271 Da / 分子数: 1 / 断片: BCL-2, UNP RESIDUES 1-155 / 由来タイプ: 組換発現 由来: (組換発現) Deerpox virus (strain W-1170-84) (ウイルス) 株: W-1170-84 / 遺伝子: DpV84gp022 / プラスミド: pDUET / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q08FF8, UniProt: Q08FX8*PLUS |
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#2: タンパク質・ペプチド | 分子量: 3274.691 Da / 分子数: 1 / 断片: BH3, UNP RESIDUES 141-166 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: O43521 |
#3: 水 | ChemComp-HOH / |
配列の詳細 | STRUCTURE FROM CONSTRUCT RESIDUES 1-155 |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 2.07 Å3/Da / 溶媒含有率: 40.7 % / 解説: IODINE DERIVATIVE |
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結晶化 | pH: 5.5 詳細: 17% PEG 8000, 0.2M MES PH 5.5, 0.2M AMMONIUM SULPHATE |
-データ収集
回折 | 平均測定温度: 100 K | |||||||||
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放射光源 | 由来: シンクロトロン / サイト: Australian Synchrotron / ビームライン: MX2 / 波長: 0.95370, 1.5498 | |||||||||
検出器 | タイプ: ADSC QUANTUM 315r / 検出器: CCD / 日付: 2013年3月1日 / 詳細: SILICON MIRRORS (ADAPTIVE AND U-BENT) | |||||||||
放射 | モノクロメーター: DOUBLE CRYSTAL MONOCHROMATOR (SI111) プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray | |||||||||
放射波長 |
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反射 | 解像度: 2.7→94.39 Å / Num. obs: 6039 / % possible obs: 100 % / Observed criterion σ(I): 2 / 冗長度: 10 % / Biso Wilson estimate: 65.25 Å2 / Rmerge(I) obs: 0.08 / Net I/σ(I): 19.5 | |||||||||
反射 シェル | 解像度: 2.7→2.83 Å / 冗長度: 10.5 % / Rmerge(I) obs: 0.89 / Mean I/σ(I) obs: 2.8 / % possible all: 100 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 単一同系置換・異常分散 開始モデル: NONE 解像度: 2.7→19.99 Å / SU ML: 0.39 / σ(F): 2 / 位相誤差: 29.54 / 立体化学のターゲット値: ML 詳細: RESIDUES FROM 1 AND 2 AND FROM 138 TO 155 ARE MISSING IN DPV022. IN BIM,THE RESIDUES 50 AND 55 AS WELL AS 74-76
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 91.4 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.7→19.99 Å
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拘束条件 |
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LS精密化 シェル |
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精密化 TLS | 手法: refined / Refine-ID: X-RAY DIFFRACTION
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精密化 TLSグループ |
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