+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8d5c | |||||||||
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タイトル | anti-HIV-1 gp120-sCD4 complex antibody CG10 Fab in complex with B41-sCD4 | |||||||||
要素 |
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キーワード | VIRAL PROTEIN/Immune System / HIV-1 Env / anti-HIV-1 antibody / VIRAL PROTEIN / 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 / 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 / host cell plasma membrane / structural molecule activity / 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 | Human immunodeficiency virus 1 (ヒト免疫不全ウイルス) Human immunodeficiency virus (ヒト免疫不全ウイルス) Homo sapiens (ヒト) Mus musculus (ハツカネズミ) | |||||||||
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: 3.9 Å | |||||||||
データ登録者 | Yang, Z. / Bjorkman, P.J. / Gershoni, J.M. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: J Virol / 年: 2022 タイトル: Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers. 著者: Zhi Yang / Kim-Marie A Dam / Jonathan M Gershoni / Susan Zolla-Pazner / Pamela J Bjorkman / 要旨: Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 ...Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 and a coreceptor. CD4 binding induces rearrangements in Env trimer, resulting in a CD4-induced (CD4i) open Env conformation. Structural studies of antibodies isolated from infected donors have defined antibody-Env interactions, with one class of antibodies specifically recognizing the CD4i open Env conformation. In this study, we characterized a group of monoclonal antibodies isolated from HIV-1 infected donors (V2i MAbs) that displayed characteristics of CD4i antibodies. Binding experiments demonstrated that the V2i MAbs preferentially recognize CD4-bound open Env trimers. Structural characterizations of V2i MAb-Env-CD4 trimer complexes using single-particle cryo-electron microscopy showed recognition by V2i MAbs using different angles of approach to the gp120 V1V2 domain and the β2/β3 strands on a CD4i open conformation Env with no direct interactions of the MAbs with CD4. We also characterized CG10, a CD4i antibody that was raised in mice immunized with a gp120-CD4 complex, bound to an Env trimer plus CD4. CG10 exhibited characteristics similar to those of the V2i antibodies, i.e., recognition of the open Env conformation, but showed direct contacts to both CD4 and gp120. Structural comparisons of these and previously characterized CD4i antibody interactions with Env provide a suggested mechanism for how these antibodies are elicited during HIV-1 infection. The RV144 HIV-1 clinical vaccination trial showed modest protection against viral infection. Antibody responses to the V1V2 region of HIV-1 Env gp120 were correlated inversely with the risk of infection, and data from three other clinical vaccine trials suggested a similar signal. In addition, antibodies targeting V1V2 have been correlated with protections from simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infections in nonhuman primates. We structurally characterized V2i antibodies directed against V1V2 isolated from HIV-1 infected humans in complex with open Env trimers bound to the host receptor CD4. We also characterized a CD4i antibody that interacts with CD4 as well as the gp120 subunit of an open Env trimer. Our study suggests how V2i and CD4i antibodies were elicited during HIV-1 infection. | |||||||||
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 | 8d5c.cif.gz | 569.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8d5c.ent.gz | 469.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8d5c.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 | 8d5c_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8d5c_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 8d5c_validation.xml.gz | 92.6 KB | 表示 | |
CIF形式データ | 8d5c_validation.cif.gz | 135.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/d5/8d5c ftp://data.pdbj.org/pub/pdb/validation_reports/d5/8d5c | HTTPS FTP |
-関連構造データ
関連構造データ | 27208MC 8d54C C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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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
#1: タンパク質 | 分子量: 17357.824 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) 株: B41 / 遺伝子: env / 細胞株 (発現宿主): CHO Flp-In (Invitrogen) 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: B3UEZ6 #2: タンパク質 | 分子量: 57702.469 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) Human immunodeficiency virus (ヒト免疫不全ウイルス) 遺伝子: env / 細胞株 (発現宿主): CHO 発現宿主: Cricetulus griseus (モンゴルキヌゲネズミ) 参照: UniProt: B3UES2 #3: タンパク質 | 分子量: 20288.055 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CD4 / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P01730 #4: 抗体 | 分子量: 24583.389 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) #5: 抗体 | 分子量: 23733.164 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) |
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-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: CG10-B41 SOSIP-sCD4 complex / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 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 / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1800 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 134746 / 対称性のタイプ: POINT |