+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6nil | ||||||
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タイトル | cryoEM structure of the truncated HIV-1 Vif/CBFbeta/A3F complex | ||||||
要素 |
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キーワード | ANTIVIRAL PROTEIN / Human antiviral restriction factor / HIV viral protein | ||||||
機能・相同性 | 機能・相同性情報 RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / 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 / base conversion or substitution editing ...RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / 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 / base conversion or substitution editing / single-stranded DNA cytosine deaminase / negative regulation of CD4-positive, alpha-beta T cell differentiation / DNA cytosine deamination / lymphocyte differentiation / cytidine to uridine editing / clearance of foreign intracellular DNA / cytidine deaminase activity / negative regulation of viral process / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / negative regulation of single stranded viral RNA replication via double stranded DNA intermediate / RUNX2 regulates genes involved in cell migration / RUNX2 regulates genes involved in differentiation of myeloid cells / Transcriptional regulation by RUNX2 / transposable element silencing / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / positive regulation of gene expression via chromosomal CpG island demethylation / myeloid cell differentiation / RUNX3 Regulates Immune Response and Cell Migration / definitive hemopoiesis / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / negative regulation of viral genome replication / 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 / RUNX3 regulates p14-ARF / positive regulation of defense response to virus by host / cell maturation / viral life cycle / virion component / P-body / Regulation of RUNX3 expression and activity / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Transcriptional regulation of granulopoiesis / protein polyubiquitination / osteoblast differentiation / Regulation of RUNX2 expression and activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / defense response to virus / Estrogen-dependent gene expression / sequence-specific DNA binding / host cell cytoplasm / transcription by RNA polymerase II / transcription coactivator activity / ribonucleoprotein complex / innate immune response / regulation of transcription by RNA polymerase II / host cell plasma membrane / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / RNA binding / zinc ion binding / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) | ||||||
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: 3.9 Å | ||||||
データ登録者 | Hu, Y. / Xiong, Y. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structural basis of antagonism of human APOBEC3F by HIV-1 Vif. 著者: Yingxia Hu / Belete A Desimmie / Henry C Nguyen / Samantha J Ziegler / Tat Cheung Cheng / John Chen / Jia Wang / Hongwei Wang / Kai Zhang / Vinay K Pathak / Yong Xiong / 要旨: HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 ...HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 interactions to reinstate the A3-catalyzed suppression of human immunodeficiency virus type 1 (HIV-1) replication is a potential approach for antiviral therapeutics. However, the molecular mechanisms by which Vif recognizes A3 proteins remain elusive. Here we report a cryo-EM structure of the Vif-targeted C-terminal domain of human A3F in complex with HIV-1 Vif and the cellular cofactor core-binding factor beta (CBFβ) at 3.9-Å resolution. The structure shows that Vif and CBFβ form a platform to recruit A3F, revealing a direct A3F-recruiting role of CBFβ beyond Vif stabilization, and captures multiple independent A3F-Vif interfaces. Together with our biochemical and cellular studies, our structural findings establish the molecular determinants that are critical for Vif-mediated neutralization of A3F and provide a comprehensive framework of how HIV-1 Vif hijacks the host protein degradation machinery to counteract viral restriction by A3F. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6nil.cif.gz | 383.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6nil.ent.gz | 315 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6nil.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 | 6nil_validation.pdf.gz | 814.8 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6nil_full_validation.pdf.gz | 822 KB | 表示 | |
XML形式データ | 6nil_validation.xml.gz | 50.6 KB | 表示 | |
CIF形式データ | 6nil_validation.cif.gz | 75.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ni/6nil ftp://data.pdbj.org/pub/pdb/validation_reports/ni/6nil | 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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-要素
#1: タンパク質 | 分子量: 24433.271 Da / 分子数: 4 / 断片: C-terminal domain 変異: Y196D, H247G, C248R, F302K, W310K, Y314A, Q315A, K355D, K358D, F363D 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: APOBEC3F / 発現宿主: Escherichia coli (大腸菌) 参照: UniProt: Q8IUX4, single-stranded DNA cytosine deaminase #2: タンパク質 | 分子量: 17851.043 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CBFB / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q13951 #3: タンパク質 | 分子量: 16736.102 Da / 分子数: 4 / 由来タイプ: 組換発現 詳細: Residues 114-157 was replaced with a 6 amino acid linker (EASEGS). The C-terminal residues 177-192 were deleted. 由来: (組換発現) Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) 遺伝子: vif / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P12504, UniProt: A0A346ARH7 #4: 化合物 | ChemComp-ZN / 研究の焦点であるリガンドがあるか | Y | |
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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 |
-試料調製
構成要素 |
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分子量 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||
試料支持 | 詳細: unspecified | ||||||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
撮影 | 電子線照射量: 56 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: REFMAC / バージョン: 5.8.0257 / 分類: 精密化 |
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CTF補正 | タイプ: NONE |
対称性 | 点対称性: D2 (2回x2回 2面回転対称) |
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 337256 / 対称性のタイプ: POINT |