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基本情報
登録情報 | データベース: PDB / ID: 8szk | ||||||
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タイトル | The cryo-EM structure of PPP2R5A/HIV-1 Vif/CBFb/EloB/EloC complex | ||||||
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![]() | VIRAL PROTEIN / HIV Vif / Cul5 E3 ligase / PPP2R5A | ||||||
機能・相同性 | ![]() negative regulation of lipid kinase activity / RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / RUNX1 regulates transcription of genes involved in interleukin signaling / RUNX2 regulates bone development / core-binding factor complex / RUNX1 regulates expression of components of tight junctions / positive regulation of CD8-positive, alpha-beta T cell differentiation / RUNX2 regulates chondrocyte maturation / negative regulation of CD4-positive, alpha-beta T cell differentiation ...negative regulation of lipid kinase activity / RUNX3 regulates RUNX1-mediated transcription / RUNX1 regulates transcription of genes involved in BCR signaling / RUNX1 regulates transcription of genes involved in interleukin signaling / RUNX2 regulates bone development / core-binding factor complex / RUNX1 regulates expression of components of tight junctions / positive regulation of CD8-positive, alpha-beta T cell differentiation / RUNX2 regulates chondrocyte maturation / negative regulation of CD4-positive, alpha-beta T cell differentiation / protein phosphatase type 2A complex / lymphocyte differentiation / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / RUNX2 regulates genes involved in cell migration / RUNX2 regulates genes involved in differentiation of myeloid cells / protein phosphatase regulator activity / Transcriptional regulation by RUNX2 / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / myeloid cell differentiation / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / target-directed miRNA degradation / RUNX3 Regulates Immune Response and Cell Migration / elongin complex / VCB complex / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / definitive hemopoiesis / M band / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / negative regulation of protein localization to plasma membrane / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / CTLA4 inhibitory signaling / Platelet sensitization by LDL / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / RUNX2 regulates osteoblast differentiation / protein phosphatase activator activity / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / phosphoprotein phosphatase activity / RUNX3 regulates p14-ARF / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / chromosome, centromeric region / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / positive regulation of protein dephosphorylation / cell maturation / viral life cycle / Resolution of Sister Chromatid Cohesion / RNA Polymerase II Pre-transcription Events / protein dephosphorylation / transcription corepressor binding / virion component / transcription elongation by RNA polymerase II / RHO GTPases Activate Formins / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / Vif-mediated degradation of APOBEC3G / RAF activation / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Degradation of beta-catenin by the destruction complex / PKR-mediated signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / kinase binding / Z disc / Transcriptional regulation of granulopoiesis / osteoblast differentiation / protein polyubiquitination / Negative regulation of MAPK pathway / Separation of Sister Chromatids / Regulation of RUNX2 expression and activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / ubiquitin-dependent protein catabolic process / protein-containing complex assembly 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: 3.58 Å | ||||||
![]() | Hu, Y. / Xiong, Y. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into PPP2R5A degradation by HIV-1 Vif. 著者: Yingxia Hu / Krista A Delviks-Frankenberry / Chunxiang Wu / Fidel Arizaga / Vinay K Pathak / Yong Xiong / ![]() 要旨: HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFβ to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the ...HIV-1 Vif recruits host cullin-RING-E3 ubiquitin ligase and CBFβ to degrade the cellular APOBEC3 antiviral proteins through diverse interactions. Recent evidence has shown that Vif also degrades the regulatory subunits PPP2R5(A-E) of cellular protein phosphatase 2A to induce G2/M cell cycle arrest. As PPP2R5 proteins bear no functional or structural resemblance to A3s, it is unclear how Vif can recognize different sets of proteins. Here we report the cryogenic-electron microscopy structure of PPP2R5A in complex with HIV-1 Vif-CBFβ-elongin B-elongin C at 3.58 Å resolution. The structure shows PPP2R5A binds across the Vif molecule, with biochemical and cellular studies confirming a distinct Vif-PPP2R5A interface that partially overlaps with those for A3s. Vif also blocks a canonical PPP2R5A substrate-binding site, indicating that it suppresses the phosphatase activities through both degradation-dependent and degradation-independent mechanisms. Our work identifies critical Vif motifs regulating the recognition of diverse A3 and PPP2R5A substrates, whereby disruption of these host-virus protein interactions could serve as potential targets for HIV-1 therapeutics. | ||||||
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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 | ![]() | 179.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 137.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 982.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1006.2 KB | 表示 | |
XML形式データ | ![]() | 37 KB | 表示 | |
CIF形式データ | ![]() | 53.6 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 | ![]() 40919MC 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: 13147.781 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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#2: タンパク質 | 分子量: 10843.420 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#3: タンパク質 | 分子量: 23644.197 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#4: タンパク質 | 分子量: 20982.240 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: vif / 発現宿主: ![]() ![]() |
#5: タンパク質 | 分子量: 56266.555 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-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: PPP2R5A in complex with HIV-1 Vif/CBFb/EloB/EloC / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES | ||||||||||||
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分子量 | 実験値: NO | ||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||
緩衝液 | pH: 8 | ||||||||||||
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): 2000 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.58 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 500511 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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