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基本情報
登録情報 | データベース: PDB / ID: 7zlk | ||||||||||||
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タイトル | AMC009 SOSIPv5.2 in complex with Fabs ACS101 and ACS124 | ||||||||||||
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生物種 | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
手法 | ![]() ![]() ![]() | ||||||||||||
![]() | van Schooten, J. / Ozorowski, G. / Ward, A. | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer. 著者: Jelle van Schooten / Anna Schorcht / Elinaz Farokhi / Jeffrey C Umotoy / Hongmei Gao / Tom L G M van den Kerkhof / Jessica Dorning / Tim G Rijkhold Meesters / Patricia van der Woude / Judith ...著者: Jelle van Schooten / Anna Schorcht / Elinaz Farokhi / Jeffrey C Umotoy / Hongmei Gao / Tom L G M van den Kerkhof / Jessica Dorning / Tim G Rijkhold Meesters / Patricia van der Woude / Judith A Burger / Tom Bijl / Riham Ghalaiyini / Alba Torrents de la Peña / Hannah L Turner / Celia C Labranche / Robyn L Stanfield / Devin Sok / Hanneke Schuitemaker / David C Montefiori / Dennis R Burton / Gabriel Ozorowski / Michael S Seaman / Ian A Wilson / Rogier W Sanders / Andrew B Ward / Marit J van Gils / ![]() ![]() 要旨: Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely ...Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses. | ||||||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 516.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 436.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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
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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
-AMC009 SOSIPv5.2 envelope glycoprotein ... , 2種, 6分子 ACDBEF
#1: タンパク質 | 分子量: 54145.488 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 発現宿主: ![]() ![]() #2: タンパク質 | 分子量: 17423.865 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 発現宿主: ![]() ![]() |
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-抗体 , 4種, 10分子 HOQLPRMSNT
#3: 抗体 | 分子量: 13280.985 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #4: 抗体 | 分子量: 12186.664 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #5: 抗体 | 分子量: 13774.439 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #6: 抗体 | 分子量: 11668.917 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
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-糖 , 7種, 37分子 ![](data/chem/img/NAG.gif)
#7: 多糖 | ![]() #8: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ![]() #9: 多糖 | ![]() #10: 多糖 | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ![]() #11: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ![]() #12: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ![]() #13: 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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-実験情報
-実験
実験 | 手法: ![]() |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: ![]() |
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試料調製
構成要素 | 名称: AMC009 SOSIPv5.2 in complex with Fabs ACS114 and ACS122 タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT | ||||||||||||||||
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分子量 |
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由来(天然) | 生物種: ![]() ![]() ![]() | ||||||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色![]() ![]() | ||||||||||||||||
急速凍結![]() | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TALOS ARCTICA |
電子銃 | 電子線源![]() ![]() |
電子レンズ | モード: BRIGHT FIELD![]() |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 49.3 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) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 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![]() | ||||||||||||||||||||||||
3次元再構成![]() | 解像度: 3.99 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 159597 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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