+
データを開く
-
基本情報
| 登録情報 | データベース: PDB / ID: 7mxe | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Ab1245 Fab in complex with BG505 SOSIP.664 and 8ANC195 Fab | |||||||||
要素 |
| |||||||||
キーワード | ANTIVIRAL PROTEIN/VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / non-neutralizing / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-VIRAL PROTEIN complex | |||||||||
| 機能・相同性 | 機能・相同性情報symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell ...symbiont-mediated perturbation of host defense response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / membrane 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト)![]() Human immunodeficiency virus 1 (ヒト免疫不全ウイルス)![]() | |||||||||
| 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: 3.7 Å | |||||||||
データ登録者 | Abernathy, M.E. / Bjorkman, P.J. | |||||||||
| 資金援助 | 米国, 2件
| |||||||||
引用 | ジャーナル: NPJ Vaccines / 年: 2021タイトル: Antibody elicited by HIV-1 immunogen vaccination in macaques displaces Env fusion peptide and destroys a neutralizing epitope. 著者: Morgan E Abernathy / Harry B Gristick / Jost Vielmetter / Jennifer R Keeffe / Priyanthi N P Gnanapragasam / Yu E Lee / Amelia Escolano / Rajeev Gautam / Michael S Seaman / Malcolm A Martin / ...著者: Morgan E Abernathy / Harry B Gristick / Jost Vielmetter / Jennifer R Keeffe / Priyanthi N P Gnanapragasam / Yu E Lee / Amelia Escolano / Rajeev Gautam / Michael S Seaman / Malcolm A Martin / Michel C Nussenzweig / Pamela J Bjorkman / ![]() 要旨: HIV-1 vaccine design aims to develop an immunogen that elicits broadly neutralizing antibodies against a desired epitope, while eliminating responses to off-target regions of HIV-1 Env. We report ...HIV-1 vaccine design aims to develop an immunogen that elicits broadly neutralizing antibodies against a desired epitope, while eliminating responses to off-target regions of HIV-1 Env. We report characterization of Ab1245, an off-target antibody against the Env gp120-gp41 interface, from V3-glycan patch immunogen-primed and boosted macaques. A 3.7 Å cryo-EM structure of an Ab1245-Env complex reveals one Ab1245 Fab binding asymmetrically to Env trimer at the gp120-gp41 interface using its long CDRH3 to mimic regions of gp41. The mimicry includes positioning of a CDRH3 methionine into the gp41 tryptophan clasp, resulting in displacement of the fusion peptide and fusion peptide-proximal region. Despite fusion peptide displacement, Ab1245 is non-neutralizing even at high concentrations, raising the possibility that only two fusion peptides per trimer are required for viral-host membrane fusion. These structural analyses facilitate immunogen design to prevent elicitation of Ab1245-like antibodies that block neutralizing antibodies against the fusion peptide. | |||||||||
| 履歴 |
|
-
構造の表示
| ムービー |
ムービービューア |
|---|---|
| 構造ビューア | 分子: Molmil Jmol/JSmol |
-
ダウンロードとリンク
-
ダウンロード
| PDBx/mmCIF形式 | 7mxe.cif.gz | 561.1 KB | 表示 | PDBx/mmCIF形式 |
|---|---|---|---|---|
| PDB形式 | pdb7mxe.ent.gz | 449.9 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 7mxe.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
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mx/7mxe ftp://data.pdbj.org/pub/pdb/validation_reports/mx/7mxe | HTTPS FTP |
|---|
-関連構造データ
-
リンク
-
集合体
| 登録構造単位 | ![]()
|
|---|---|
| 1 |
|
-
要素
-タンパク質 , 2種, 6分子 CDFGJP
| #3: タンパク質 | 分子量: 17146.482 Da / 分子数: 3 / 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 / Cell (発現宿主): CHO 発現宿主: ![]() 参照: UniProt: Q2N0S6 #4: タンパク質 | 分子量: 53864.086 Da / 分子数: 3 / 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 / Cell (発現宿主): CHO 発現宿主: ![]() 参照: UniProt: Q2N0S6 |
|---|
-抗体 , 4種, 8分子 AHMBLORW
| #1: 抗体 | 分子量: 26153.283 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)#2: 抗体 | 分子量: 23460.047 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)#5: 抗体 | | 分子量: 28154.803 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() Homo sapiens (ヒト)#6: 抗体 | | 分子量: 25306.172 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() Homo sapiens (ヒト) |
|---|
-糖 , 8種, 55分子 
| #7: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #8: 多糖 | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #9: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D- ...alpha-D-mannopyranose-(1-2)-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 | #10: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-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 | #11: 多糖 | #12: 多糖 | #13: 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 #14: 糖 | ChemComp-NAG / |
|---|
-詳細
| 研究の焦点であるリガンドがあるか | N |
|---|---|
| Has protein modification | Y |
-実験情報
-実験
| 実験 | 手法: 電子顕微鏡法 |
|---|---|
| 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 |
| ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 分子量 | 値: .5 MDa / 実験値: NO | ||||||||||||||||||||||||||||||
| 由来(天然) |
| ||||||||||||||||||||||||||||||
| 由来(組換発現) |
| ||||||||||||||||||||||||||||||
| 緩衝液 | pH: 8 | ||||||||||||||||||||||||||||||
| 緩衝液成分 |
| ||||||||||||||||||||||||||||||
| 試料 | 濃度: 4.7 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Ab1245 was incubated with BG505 SOSIP at room temperature for 3 hours, after which 8ANC195 Fab was added and the complex was incubated overnight at RT before SEC purification and concentration to 4.7 mg/mL. | ||||||||||||||||||||||||||||||
| 試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R2/2 | ||||||||||||||||||||||||||||||
| 急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 295 K / 詳細: 0 blot force, 3 second blot time, 3 uL sample added |
-
電子顕微鏡撮影
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
|---|---|
| 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): 105000 X / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 800 nm |
| 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: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 実像数: 2307 |
-
解析
| EMソフトウェア |
| ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
| 粒子像の選択 | 選択した粒子像数: 421388 | ||||||||||||||||||||||||||||||
| 対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 172731 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||
| 原子モデル構築 | プロトコル: RIGID BODY FIT | ||||||||||||||||||||||||||||||
| 原子モデル構築 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
|
ムービー
コントローラー
万見について




Homo sapiens (ヒト)
Human immunodeficiency virus 1 (ヒト免疫不全ウイルス)

米国, 2件
引用
UCSF Chimera








PDBj








