SASDC63: Fowlpox Virus FPV039 antiapoptotic Bcl-2 viral protein in complex...

基本情報

登録情報

データベース: SASBDB / ID: SASDC63

試料

Fowlpox Virus FPV039 antiapoptotic Bcl-2 viral protein in complex with BaK BH3 peptide (FPV039:BAK)

• Bcl-2-like protein FPV039 (protein), FPV039, Fowlpox virus (strain NVSL)
• Uncharacterized protein (BAK1) (protein), Bak, Gallus gallus

機能・相同性

分子機能:

Activation and oligomerization of BAK protein / Release of apoptotic factors from the mitochondria / : / response to mycotoxin / B cell negative selection / BAK complex / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / apoptotic process involved in blood vessel morphogenesis / response to fungus / negative regulation of endoplasmic reticulum calcium ion concentration / limb morphogenesis / post-embryonic camera-type eye morphogenesis / establishment or maintenance of transmembrane electrochemical gradient / B cell apoptotic process / activation of cysteine-type endopeptidase activity / positive regulation of endoplasmic reticulum unfolded protein response / regulation of mitochondrial membrane permeability / fibroblast apoptotic process / mitochondrial fusion / myeloid cell homeostasis / positive regulation of calcium ion transport into cytosol / pore complex / thymocyte apoptotic process / negative regulation of peptidyl-serine phosphorylation / vagina development / B cell homeostasis / host cell mitochondrion / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / blood vessel remodeling / extrinsic apoptotic signaling pathway in absence of ligand / release of cytochrome c from mitochondria / regulation of mitochondrial membrane potential / response to gamma radiation / positive regulation of protein-containing complex assembly / cellular response to mechanical stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / cellular response to UV / regulation of apoptotic process / mitochondrial outer membrane / transmembrane transporter binding / cell population proliferation / regulation of cell cycle / positive regulation of apoptotic process / protein heterodimerization activity / endoplasmic reticulum / protein homodimerization activity / cytosol

ドメイン・相同性:

Apoptosis regulator BAK / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Apoptosis regulator, Bcl-2, BH2 motif, conserved site / Apoptosis regulator, Bcl-2 family BH2 motif signature. / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl-2 family / Bcl-2, Bcl-2 homology region 1-3 / Bcl2-like / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily

構成要素:

Uncharacterized protein / Apoptosis regulator Bcl-2 homolog

• 生物種: Fowlpox virus (strain NVSL) (ウイルス); Gallus gallus (ニワトリ)
• 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-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.

登録者

• Sofia Caria

モデル

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
• 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
• 検出器: 名称: Pilatus 1M

スキャン

タイトル: Fowlpox Virus FPV039 antiapoptotic Bcl-2 viral protein in complex with BaK BH3 peptide (FPV039:BAK)
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 /

	Min	Max
Q	0.0106	0.6185

結果

Experimental MW: 17.9 kDa / カーブのタイプ: single_conc

	Guinier	Guinier error
前方散乱 I0	0.104031	0.0002
慣性半径, Rg	1.96 nm	0.006

	Min	Max
Guinier point	38	70