+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8gje | ||||||
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タイトル | HIV-1 Env subtype C CZA97.12 SOSIP.664 in complex with 3BNC117 Fab | ||||||
要素 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / HIV Envelope / SOSIP / broadly neutralizing antibody / clade C / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | 機能・相同性情報 : / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane ...: / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / 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 | 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: 3.4 Å | ||||||
データ登録者 | Ozorowski, G. / Lee, J.H. / Ward, A.B. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: PLoS Pathog / 年: 2023 タイトル: Glycan heterogeneity as a cause of the persistent fraction in HIV-1 neutralization. 著者: Rajesh P Ringe / Philippe Colin / Gabriel Ozorowski / Joel D Allen / Anila Yasmeen / Gemma E Seabright / Jeong Hyun Lee / Aleksandar Antanasijevic / Kimmo Rantalainen / Thomas Ketas / John P ...著者: Rajesh P Ringe / Philippe Colin / Gabriel Ozorowski / Joel D Allen / Anila Yasmeen / Gemma E Seabright / Jeong Hyun Lee / Aleksandar Antanasijevic / Kimmo Rantalainen / Thomas Ketas / John P Moore / Andrew B Ward / Max Crispin / P J Klasse / 要旨: Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the ...Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the persistent fraction of infectivity at maximum neutralization, which may also influence preventive efficacy of active or passive immunization and the therapeutic outcome of the latter. Many NAbs neutralize HIV-1 CZA97.012, a clone of a Clade-C isolate, to ~100%. But here NAb PGT151, directed to a fusion-peptide epitope, left a persistent fraction of 15%. NAb PGT145, ligating the Env-trimer apex, left no detectable persistent fraction. The divergence in persistent fractions was further analyzed by depletion of pseudoviral populations of the most PGT151- and PGT145-reactive virions. Thereby, neutralization by the non-depleting NAb increased, whereas neutralization by the depleting NAb decreased. Furthermore, depletion by PGT151 increased sensitivity to autologous neutralization by sera from rabbits immunized with soluble native-like CZA97.012 trimer: substantial persistent fractions were reduced. NAbs in these sera target epitopes comprising residue D411 at the V4-β19 transition in a defect of the glycan shield on CZA97.012 Env. NAb binding to affinity-fractionated soluble native-like CZA97.012 trimer differed commensurately with neutralization in analyses by ELISA and surface plasmon resonance. Glycan differences between PGT151- and PGT145-purified trimer fractions were then demonstrated by mass spectrometry, providing one explanation for the differential antigenicity. These differences were interpreted in relation to a new structure at 3.4-Å resolution of the soluble CZA97.012 trimer determined by cryo-electron microscopy. The trimer adopted a closed conformation, refuting apex opening as the cause of reduced PGT145 binding to the PGT151-purified form. The evidence suggests that differences in binding and neutralization after trimer purification or pseudovirus depletion with PGT145 or PGT151 are caused by variation in glycosylation, and that some glycan variants affect antigenicity through direct effects on antibody contacts, whereas others act allosterically. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8gje.cif.gz | 532.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8gje.ent.gz | 430.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8gje.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 | 8gje_validation.pdf.gz | 3.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8gje_full_validation.pdf.gz | 3.2 MB | 表示 | |
XML形式データ | 8gje_validation.xml.gz | 77.3 KB | 表示 | |
CIF形式データ | 8gje_validation.cif.gz | 116.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/gj/8gje ftp://data.pdbj.org/pub/pdb/validation_reports/gj/8gje | HTTPS FTP |
-関連構造データ
関連構造データ | 40088MC 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 (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
-集合体
登録構造単位 |
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1 |
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-要素
-CZA97.12 SOSIP.664 Envelope glycoprotein ... , 2種, 6分子 ACDBEF
#1: タンパク質 | 分子量: 56995.121 Da / 分子数: 3 変異: A501C, and also cleavage site mutations to introduce a furin cleavage site 由来タイプ: 組換発現 由来: (組換発現) Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) 遺伝子: env / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q994M9 #2: タンパク質 | 分子量: 17279.670 Da / 分子数: 3 / 変異: L535M, I559P, T605C, Q567K / 由来タイプ: 組換発現 由来: (組換発現) Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) 遺伝子: env / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q994M9 |
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-抗体 / タンパク質 , 2種, 6分子 HGILJK
#3: 抗体 | 分子量: 24656.484 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) #4: タンパク質 | 分子量: 23022.658 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト) |
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-糖 , 5種, 60分子
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: 多糖 | #7: 多糖 | #8: 多糖 | #9: 糖 | ChemComp-NAG / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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Has protein modification | Y |
-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 | 名称: CZA97.12 SOSIP.664 in complex with 3BNC117 Fab / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES | ||||||||||||||||||||
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分子量 | 値: 0.57 MDa / 実験値: NO | ||||||||||||||||||||
緩衝液 | pH: 7.4 / 詳細: Detergent added shortly before freezing | ||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのタイプ: C-flat-2/2 | ||||||||||||||||||||
急速凍結 | 装置: HOMEMADE PLUNGER / 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 / 倍率(公称値): 22500 X / 最大 デフォーカス(公称値): 2700 nm / 最小 デフォーカス(公称値): 1000 nm / Cs: 2.7 mm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 58 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 実像数: 1142 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||||||||||
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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: C3 (3回回転対称) | ||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 79261 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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