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基本情報
登録情報 | データベース: PDB / ID: 8cx2 | ||||||
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タイトル | Cryo-EM structure of human APOBEC3G/HIV-1 Vif/CBFbeta/ELOB/ELOC dimeric complex in State 2 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM/RNA / Viral protein / RNA binding protein / Complex / Ubiquitin E3 ligase / VIRAL PROTEIN-IMMUNE SYSTEM-RNA complex | ||||||
機能・相同性 | ![]() RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / RUNX1 regulates transcription of genes involved in BCR signaling / dCTP deaminase activity / cytidine deamination / 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 ...RUNX3 regulates RUNX1-mediated transcription / apolipoprotein B mRNA editing enzyme complex / RUNX1 regulates transcription of genes involved in BCR signaling / dCTP deaminase activity / cytidine deamination / 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 / cytidine deaminase activity / RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) / negative regulation of viral process / 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 / retrotransposon silencing / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / myeloid cell differentiation / target-directed miRNA degradation / RUNX3 Regulates Immune Response and Cell Migration / elongin complex / VCB complex / definitive hemopoiesis / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of RUNX1 Expression and Activity / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / 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 / APOBEC3G mediated resistance to HIV-1 infection / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / RUNX3 regulates p14-ARF / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / cell maturation / 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 / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / positive regulation of defense response to virus by host / RNA Polymerase II Pre-transcription Events / viral life cycle / transcription corepressor binding / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / Transcriptional regulation of granulopoiesis / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Regulation of RUNX3 expression and activity / P-body / 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 / virion component / osteoblast differentiation / protein polyubiquitination / Regulation of RUNX2 expression and activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / protein-containing complex assembly / sequence-specific DNA binding / defense response to virus / Estrogen-dependent gene expression / transcription coactivator activity / host cell cytoplasm / transcription by RNA polymerase II / protein ubiquitination / ribonucleoprotein complex / innate immune response / ubiquitin protein ligase binding / 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 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: 3.2 Å | ||||||
![]() | Li, Y. / Langley, C. / Azumaya, C.M. / Echeverria, I. / Chesarino, N.M. / Emerman, M. / Cheng, Y. / Gross, J.D. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The structural basis for HIV-1 Vif antagonism of human APOBEC3G. 著者: Yen-Li Li / Caroline A Langley / Caleigh M Azumaya / Ignacia Echeverria / Nicholas M Chesarino / Michael Emerman / Yifan Cheng / John D Gross / ![]() 要旨: The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles. ...The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles. The lentiviruses encode a protein, Vif, that antagonizes A3 family members by targeting them for degradation. Diversification of A3 allows host escape from Vif whereas adaptations in Vif enable cross-species transmission of primate lentiviruses. How this 'molecular arms race' plays out at the structural level is unknown. Here, we report the cryogenic electron microscopy structure of human APOBEC3G (A3G) bound to HIV-1 Vif, and the hijacked cellular proteins that promote ubiquitin-mediated proteolysis. A small surface explains the molecular arms race, including a cross-species transmission event that led to the birth of HIV-1. Unexpectedly, we find that RNA is a molecular glue for the Vif-A3G interaction, enabling Vif to repress A3G by ubiquitin-dependent and -independent mechanisms. Our results suggest a model in which Vif antagonizes A3G by intercepting it in its most dangerous form for the virus-when bound to RNA and on the pathway to packaging-to prevent viral restriction. By engaging essential surfaces required for restriction, Vif exploits a vulnerability in A3G, suggesting a general mechanism by which RNA binding helps to position key residues necessary for viral antagonism of a host antiviral gene. | ||||||
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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 | ![]() | 341.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 273.8 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 27034MC ![]() 8cx0C ![]() 8cx1C 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
-タンパク質 , 5種, 10分子 AFBGCHDIEJ
#1: タンパク質 | 分子量: 50034.598 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9HC16, single-stranded DNA cytosine deaminase #2: タンパク質 | 分子量: 22556.002 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: vif 発現宿主: ![]() ![]() 参照: UniProt: Q77YG0 #3: タンパク質 | 分子量: 21542.188 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q13951 #4: タンパク質 | 分子量: 13147.781 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q15370 #5: タンパク質 | 分子量: 12485.135 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q15369 |
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-RNA鎖 , 2種, 2分子 KL
#6: RNA鎖 | 分子量: 2871.814 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() |
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#7: RNA鎖 | 分子量: 2825.735 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() |
-非ポリマー , 1種, 6分子 ![](data/chem/img/ZN.gif)
#8: 化合物 | ChemComp-ZN / |
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-詳細
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 |
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試料調製
構成要素 | 名称: HIV-1 Vif-E3 ligase substrate receptor (VCBC) in complex with human APOBEC3G and RNA タイプ: COMPLEX / Entity ID: #1-#7 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7 |
試料 | 濃度: 0.46 mg/ml / 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 / 倍率(公称値): 105000 X / 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 / Cs: 2.7 mm |
撮影 | 電子線照射量: 68 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 46083 / 対称性のタイプ: POINT |