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基本情報
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タイトル | Cryo-EM structure of BG505 SOSIP HIV-1 Env trimer in complex with CD4 receptor (D1D2) and broadly neutralizing darpin bnD.9 | |||||||||
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![]() | HIV / Env / Broadly Neutralizing / Darpin / CD4 / VIRAL PROTEIN | |||||||||
機能・相同性 | ![]() helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / positive regulation of kinase activity / regulation of T cell activation / extracellular matrix structural constituent / T cell receptor complex / Other interleukin signaling / enzyme-linked receptor protein signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / regulation of calcium ion transport / macrophage differentiation / Generation of second messenger molecules / T cell differentiation / PD-1 signaling / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of establishment of T cell polarity / T cell activation / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / clathrin-coated endocytic vesicle membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / transmembrane signaling receptor activity / Cargo recognition for clathrin-mediated endocytosis / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of T cell activation / Clathrin-mediated endocytosis / virus receptor activity / Downstream TCR signaling / MHC class II protein complex binding / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / clathrin-dependent endocytosis of virus by host cell / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / cell surface receptor signaling pathway / positive regulation of viral entry into host cell / early endosome / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / membrane raft / immune response / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / positive regulation of DNA-templated transcription / virion attachment to host cell / protein kinase binding / apoptotic process / enzyme binding / structural molecule activity / host cell plasma membrane / virion membrane / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.87 Å | |||||||||
![]() | Cerutti G / Gorman J | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization. 著者: Matthias Glögl / Nikolas Friedrich / Gabriele Cerutti / Thomas Lemmin / Young D Kwon / Jason Gorman / Liridona Maliqi / Peer R E Mittl / Maria C Hesselman / Daniel Schmidt / Jacqueline Weber ...著者: Matthias Glögl / Nikolas Friedrich / Gabriele Cerutti / Thomas Lemmin / Young D Kwon / Jason Gorman / Liridona Maliqi / Peer R E Mittl / Maria C Hesselman / Daniel Schmidt / Jacqueline Weber / Caio Foulkes / Adam S Dingens / Tatsiana Bylund / Adam S Olia / Raffaello Verardi / Thomas Reinberg / Nicolas S Baumann / Peter Rusert / Birgit Dreier / Lawrence Shapiro / Peter D Kwong / Andreas Plückthun / Alexandra Trkola / ![]() ![]() 要旨: The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows ...The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1. | |||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 117.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.9 KB 16.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 123.2 KB | ||
その他 | ![]() | 118 MB | ||
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 | ![]() 7txdMC ![]() 7z7cC ![]() 8aedC M: このマップから作成された原子モデル 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
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.07 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: Local refinement map
ファイル | emd_26157_additional_1.map | ||||||||||||
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注釈 | Local refinement map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : BG505 SOSIP HIV-1 Env trimer in complex with CD4 receptor (D1D2) ...
全体 | 名称: BG505 SOSIP HIV-1 Env trimer in complex with CD4 receptor (D1D2) and broadly neutralizing darpin bnD.9 |
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要素 |
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-超分子 #1: BG505 SOSIP HIV-1 Env trimer in complex with CD4 receptor (D1D2) ...
超分子 | 名称: BG505 SOSIP HIV-1 Env trimer in complex with CD4 receptor (D1D2) and broadly neutralizing darpin bnD.9 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Envelope glycoprotein gp120
分子 | 名称: Envelope glycoprotein gp120 / タイプ: protein_or_peptide / ID: 1 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 54.064277 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT ...文字列: AENLWVTVYY GVPVWKDAET TLFCASDAKA YETEKHNVWA THACVPTDPN PQEIHLENVT EEFNMWKNNM VEQMHTDIIS LWDQSLKPC VKLTPLCVTL QCTNVTNNIT DDMRGELKNC SFNMTTELRD KKQKVYSLFY RLDVVQINEN QGNRSNNSNK E YRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC KDKKFNGTGP CPSVSTVQCT HGIKPVVSTQ LLLNGSLAEE EV MIRSENI TNNAKNILVQ FNTPVQINCT RPNNNTRKSI RIGPGQAFYA TGDIIGDIRQ AHCNVSKATW NETLGKVVKQ LRK HFGNNT IIRFANSSGG DLEVTTHSFN CGGEFFYCNT SGLFNSTWIS NTSVQGSNST GSNDSITLPC RIKQIINMWQ RIGQ AMYAP PIQGVIRCVS NITGLILTRD GGSTNSTTET FRPGGGDMRD NWRSELYKYK VVKIEPLGVA PTRCKRRVVG RRRRR R UniProtKB: Envelope glycoprotein gp160 |
-分子 #2: Envelope glycoprotein gp41
分子 | 名称: Envelope glycoprotein gp41 / タイプ: protein_or_peptide / ID: 2 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 17.146482 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD UniProtKB: Envelope glycoprotein gp160 |
-分子 #3: T-cell surface glycoprotein CD4
分子 | 名称: T-cell surface glycoprotein CD4 / タイプ: protein_or_peptide / ID: 3 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 20.50326 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPLI IKNLKIEDSD TYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ GGKTLSVSQL ELQDSGTWTC T VLQNQKKV EFKIDIVVLA FQKASNT UniProtKB: T-cell surface glycoprotein CD4 |
-分子 #4: Broadly neutralizing darpin bnd.9
分子 | 名称: Broadly neutralizing darpin bnd.9 / タイプ: protein_or_peptide / ID: 4 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 21.214891 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GLNDIFEAQK IEWHEGSGGS DLGKKLLEAA YYGQLDEVRI LMANGADVNA VDVHGITPLH LAAYFGHLEI VEVLLKTGAD VNARDNRGI TPLHLAAAMG HLEIVEVLLK AGADVNAFDE AGDTPLHLAA LKGHLEIVEV LLKHGADVNA QDKFGKTAFD I SIDNGNED ...文字列: GLNDIFEAQK IEWHEGSGGS DLGKKLLEAA YYGQLDEVRI LMANGADVNA VDVHGITPLH LAAYFGHLEI VEVLLKTGAD VNARDNRGI TPLHLAAAMG HLEIVEVLLK AGADVNAFDE AGDTPLHLAA LKGHLEIVEV LLKHGADVNA QDKFGKTAFD I SIDNGNED IAEVLQKAAK LNLEVLFQGP HHHHHHHH |
-分子 #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 9 / コピー数: 30 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 42.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.87 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 115325 |
初期 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |
最終 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |