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試料 | Fowlpox Virus FPV039 antiapoptotic Bcl-2 viral protein in complex with BaK BH3 peptide (FPV039:BAK)
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| 機能・相同性 | 機能・相同性情報Activation and oligomerization of BAK protein / Release of apoptotic factors from the mitochondria / Pyroptosis / BH domain binding / symbiont-mediated suppression of host apoptosis / porin activity / host cell mitochondrion / extrinsic apoptotic signaling pathway in absence of ligand / release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway in response to DNA damage ...Activation and oligomerization of BAK protein / Release of apoptotic factors from the mitochondria / Pyroptosis / BH domain binding / symbiont-mediated suppression of host apoptosis / porin activity / host cell mitochondrion / extrinsic apoptotic signaling pathway in absence of ligand / release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway in response to DNA damage / regulation of apoptotic process / mitochondrial outer membrane 類似検索 - 分子機能 |
| 生物種 | Fowlpox virus (strain NVSL) (ウイルス)![]() |
引用 | ジャーナル: J Biol Chem / 年: 2017タイトル: Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039. 著者: Mohd Ishtiaq Anasir / Sofia Caria / Michael A Skinner / Marc Kvansakul / ![]() 要旨: Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B- ...Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies including the mimicry of prosurvival Bcl-2 proteins. One such viral prosurvival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis, we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering, and X-ray crystallography. Here, we report that the fowlpox virus prosurvival protein FPV039 promiscuously binds to cellular proapoptotic Bcl-2 and engages all major proapoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular proapoptotic Bcl-2 with affinities comparable with those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular prosurvival Bcl-2 proteins and closely mimics the structure of the prosurvival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan-Bcl-2 protein inhibitor that can engage all host BH3-only proteins, as well as Bcl-2-associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition. |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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試料
試料 | 名称: Fowlpox Virus FPV039 antiapoptotic Bcl-2 viral protein in complex with BaK BH3 peptide (FPV039:BAK) 試料濃度: 0.31-7.35 / Entity id: 631 / 632 |
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| バッファ | 名称: 20 mM trisodium citrate pH, 200 mM NaCl / pH: 6 |
| 要素 #631 | 名称: FPV039 / タイプ: protein / 記述: Bcl-2-like protein FPV039 / 分子量: 16.823 / 分子数: 1 / 由来: Fowlpox virus (strain NVSL) / 参照: UniProt: Q9J5G4 配列: MASSNMKDET YYIALNMIQN YIIEYNTNKP RKSFVIDSIS YDVLKAACKS VIKTNYNEFD IIISRNIDFN VIVTQVLEDK INWGRIITII AFCAYYSKKV KQDTSPQYYD GIISEAITDA ILSKYRSWFI DQDYWNGIRI YKN |
| 要素 #632 | 名称: Bak / タイプ: protein / 記述: Uncharacterized protein (BAK1) / 分子量: 2.805 / 分子数: 1 / 由来: Gallus gallus / 参照: UniProt: Q5F404 配列: LGSTGSQVGR RLAIIGDDIN KRYDAE |
-実験情報
| ビーム | 設備名称: Australian Synchrotron SAXS/WAXS / 地域: Melbourne / 国: Australia / 形状: Point / 線源: X-ray synchrotron / スペクトロメータ・検出器間距離: 1.6 mm | |||||||||||||||
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| 検出器 | 名称: Pilatus 1M | |||||||||||||||
| スキャン | 測定日: 2015年10月2日 / 保管温度: 20 °C / セル温度: 20 °C / 照射時間: 1 sec. / フレーム数: 30 / 単位: 1/A /
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| 結果 | Experimental MW: 17.9 kDa / カーブのタイプ: single_conc
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Fowlpox virus (strain NVSL) (ウイルス)
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