+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-29580 | ||||||||||||
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タイトル | Structure of HIV-1 BG505 SOSIP-HT2 in complex with two CD4 molecules (class I) | ||||||||||||
マップデータ | Structure of HIV-1 BG505 SOSIP-HT2 in complex with two CD4 molecules (class I) | ||||||||||||
試料 |
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キーワード | Viral protein / HIV-1 / IMMUNE SYSTEM / Viral protein-IMMUNE SYSTEM complex | ||||||||||||
機能・相同性 | 機能・相同性情報 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 / T cell receptor complex / extracellular matrix structural constituent / 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 calcium-mediated signaling / 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 interleukin-2 production / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / transmembrane signaling receptor activity / positive regulation of peptidyl-tyrosine phosphorylation / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / positive regulation of T cell activation / MHC class II protein complex binding / Clathrin-mediated endocytosis / virus receptor activity / signaling receptor activity / clathrin-dependent endocytosis of virus by host cell / positive regulation of canonical NF-kappaB signal transduction / defense response to Gram-negative bacterium / adaptive immune response / positive regulation of MAPK cascade / positive regulation of viral entry into host cell / early endosome / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / viral protein processing / cell adhesion / positive regulation of protein phosphorylation / immune response / membrane raft / 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 / apoptotic process / endoplasmic reticulum membrane / virion attachment to host cell / protein kinase binding / host cell plasma membrane / structural molecule activity / positive regulation of DNA-templated transcription / virion membrane / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) / Homo sapiens (ヒト) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.0 Å | ||||||||||||
データ登録者 | Fan C / Dam KA / Bjorkman PJ | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nature / 年: 2023 タイトル: Intermediate conformations of CD4-bound HIV-1 Env heterotrimers. 著者: Kim-Marie A Dam / Chengcheng Fan / Zhi Yang / Pamela J Bjorkman / 要旨: HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120 and gp41 heterodimers, has been structurally characterized in a ...HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120 and gp41 heterodimers, has been structurally characterized in a closed, prefusion conformation with closely associated gp120s and coreceptor binding sites on gp120 V3 hidden by V1V2 loops and in fully saturated CD4-bound open Env conformations with changes including outwardly rotated gp120s and displaced V1V2 loops. To investigate changes resulting from substoichiometric CD4 binding, we solved single-particle cryo-electron microscopy (cryo-EM) structures of soluble, native-like heterotrimeric Envs bound to one or two CD4 molecules. Most of the Env trimers bound to one CD4 adopted the closed, prefusion Env state, with a minority exhibiting a heterogeneous partially open Env conformation. When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on V3. The third gp120 adopted an intermediate, occluded-open state that showed gp120 outward rotation but maintained the prefusion three-stranded gp120 bridging sheet with only partial V1V2 displacement and V3 exposure. We conclude that most of the engagements with one CD4 molecule were insufficient to stimulate CD4-induced conformational changes, whereas binding two CD4 molecules led to Env opening in CD4-bound protomers only. The substoichiometric CD4-bound soluble Env heterotrimer structures resembled counterparts derived from a cryo-electron tomography study of complexes between virion-bound Envs and membrane-anchored CD4 (ref. ), validating their physiological relevance. Together, these results illuminate intermediate conformations of HIV-1 Env and illustrate its structural plasticity. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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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 | emd_29580.map.gz | 168.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-29580-v30.xml emd-29580.xml | 21.1 KB 21.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_29580.png | 52.2 KB | ||
Filedesc metadata | emd-29580.cif.gz | 6.7 KB | ||
その他 | emd_29580_half_map_1.map.gz emd_29580_half_map_2.map.gz | 165.3 MB 165.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-29580 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29580 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_29580_validation.pdf.gz | 1021.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_29580_full_validation.pdf.gz | 1021.5 KB | 表示 | |
XML形式データ | emd_29580_validation.xml.gz | 14.4 KB | 表示 | |
CIF形式データ | emd_29580_validation.cif.gz | 16.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29580 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29580 | HTTPS FTP |
-関連構造データ
関連構造データ | 8fyjMC 8fyiC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_29580.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Structure of HIV-1 BG505 SOSIP-HT2 in complex with two CD4 molecules (class I) | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.832 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
-ハーフマップ: Half Map 1
ファイル | emd_29580_half_map_1.map | ||||||||||||
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注釈 | Half Map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half Map 2
ファイル | emd_29580_half_map_2.map | ||||||||||||
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注釈 | Half Map 2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : HIV-1 Env trimer BG505 SOSIP.664 in complex with two CD4 molecules
全体 | 名称: HIV-1 Env trimer BG505 SOSIP.664 in complex with two CD4 molecules |
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要素 |
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-超分子 #1: HIV-1 Env trimer BG505 SOSIP.664 in complex with two CD4 molecules
超分子 | 名称: HIV-1 Env trimer BG505 SOSIP.664 in complex with two CD4 molecules 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: Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) |
-分子 #1: Envelope glycoprotein gp160
分子 | 名称: Envelope glycoprotein gp160 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) |
分子量 | 理論値: 53.193242 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ...文字列: NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ITQACPKVSF EPIPIHYCAP AGFAILKCKD KKFNGTGPCP SVSTVQCTHG IKPVVSTQLL LNGSLAEEEV MI RSENITN NAKNILVQFN TPVQINCTRP NNNTRKSIRI GPGQWFYATG DIIGDIRQAH CNVSKATWNE TLGKVVKQLR KHF GNNTII RFANSSGGDL EVTTHSFNCG GEFFYCNTSG LFNSTWISNT SVQGSNSTGS NDSITLPCRI KQIINMWQRI GQAM YAPPI QGVIRCVSNI TGLILTRDGG STNSTTETFR PGGGDMRDNW RSELYKYKVV KIEPLGVAPT RCKRRVVGR UniProtKB: Envelope glycoprotein gp160 |
-分子 #2: Envelope glycoprotein gp160
分子 | 名称: Envelope glycoprotein gp160 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) |
分子量 | 理論値: 53.235352 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ...文字列: NLWVTVYYGV PVWKDAETTL FCASDAKAYE TEKHNVWATH ACVPTDPNPQ EIHLENVTEE FNMWKNNMVE QMHTDIISLW DQSLKPCVK LTPLCVTLQC TNVTNNITDD MRGELKNCSF NMTTELRDKK QKVYSLFYRL DVVQINENQG NRSNNSNKEY R LINCNTSA ITQACPKVSF EPIPIHYCAP AGFAILKCKD KKFNGTGPCP SVSTVQCTHG IKPVVSTQLL LNGSLAEEEV MI RSENITN NAKNILVQFN TPVQINCTRP NNNTRKSIRI GPGQWFYATG DIIGDIRQAH CNVSKATWNE TLGKVVKQLR KHF GNNTII RFANSSGGRL EVTTHSFNCG GEFFYCNTSG LFNSTWISNT SVQGSNSTGS NDSITLPCRI KQIINMWQRI GQAM YAPPI QGVIRCVSNI TGLILTRDGG STNSTTETFR PGGGDMRDNW RSELYKYKVV KIEPLGVAPT RCKRRVVGR UniProtKB: Envelope glycoprotein gp160 |
-分子 #3: Envelope glycoprotein gp41
分子 | 名称: Envelope glycoprotein gp41 / 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: Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) |
分子量 | 理論値: 17.146482 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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 #4: T-cell surface glycoprotein CD4
分子 | 名称: T-cell surface glycoprotein CD4 / タイプ: protein_or_peptide / ID: 4 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 42.325457 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPLI IKNLKIEDSD TYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ GGKTLSVSQL ELQDSGTWTC T VLQNQKKV ...文字列: KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPLI IKNLKIEDSD TYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ GGKTLSVSQL ELQDSGTWTC T VLQNQKKV EFKIDIVVLA FQKASSIVYK KEGEQVEFSF PLAFTVEKLT GSGELWWQAE RASSSKSWIT FDLKNKEVSV KR VTQDPKL QMGKKLPLHL TLPQALPQYA GSGNLTLALE AKTGKLHQEV NLVVMRATQL QKNLTCEVWG PTSPKLMLSL KLE NKEAKV SKREKAVWVL NPEAGMWQCL LSDSGQVLLE SNIKVLPTWS TPVQPGSHHH HHH UniProtKB: T-cell surface glycoprotein CD4 |
-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: 7 / 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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 2 mg/mL |
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緩衝液 | pH: 8 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE |
-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 (6k x 4k) / 実像数: 6158 / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 105000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: RIGID BODY FIT |
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得られたモデル | PDB-8fyj: |