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基本情報
登録情報 | データベース: PDB / ID: 6mid | |||||||||
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タイトル | Cryo-EM structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195 | |||||||||
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![]() | VIRUS/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRUS-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | ![]() immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding ...immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / adaptive immune response / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / molecular adaptor activity / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / immune response / serine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / centrosome / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular space / extracellular region / ATP binding / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
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: 4 Å | |||||||||
![]() | Long, F. / Rossmann, M.G. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope. 著者: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond / ...著者: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond / James E Crowe / Michael G Rossmann / ![]() 要旨: Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and ...Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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-検証レポート
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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
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対称性 | 点対称性: (シェーンフリース記号: I (正20面体型対称)) |
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要素
#1: タンパク質 | 分子量: 54444.051 Da / 分子数: 3 / 断片: UNP residues 291-794 / 由来タイプ: 天然 由来: (天然) ![]() 株: isolate ZIKV/Human/French Polynesia/10087PF/2013 / 参照: UniProt: A0A024B7W1 #2: タンパク質 | 分子量: 8496.883 Da / 分子数: 3 / 断片: UNP residues 216-290 / 由来タイプ: 天然 由来: (天然) ![]() 株: isolate ZIKV/Human/French Polynesia/10087PF/2013 / 参照: UniProt: A0A024B7W1 #3: 抗体 | | 分子量: 14148.739 Da / 分子数: 1 / 断片: Fab variable domain / 由来タイプ: 天然 / 由来: (天然) ![]() #4: 抗体 | | 分子量: 11750.902 Da / 分子数: 1 / 断片: Fab variable domain / 由来タイプ: 天然 / 由来: (天然) ![]() #5: 多糖 | |
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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 |
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試料調製
構成要素 |
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分子量 | 単位: MEGADALTONS / 実験値: NO | ||||||||||||||||||||||||||||
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ウイルスについての詳細 | 中空か: NO / エンベロープを持つか: YES / 単離: STRAIN / タイプ: VIRION | ||||||||||||||||||||||||||||
緩衝液 | pH: 8 / 詳細: NTE buffer at pH 8.0 | ||||||||||||||||||||||||||||
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 詳細: Fab fragments were mixed with purified mature virus particles to make complexes. | ||||||||||||||||||||||||||||
試料支持 | 詳細: unspecified | ||||||||||||||||||||||||||||
急速凍結 | 装置: GATAN CRYOPLUNGE 3 / 凍結剤: ETHANE / 湿度: 90 % / 凍結前の試料温度: 298 K |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 30 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: 1691 |
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解析
EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: I (正20面体型対称) | ||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 10687 詳細: The map was masked by removing the internal nucleic acid region and the external background region. 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL 詳細: The occupancy of bound Fabs was low. Due to poor density, only the variable domain of Fab molecule was modeled and fit into one of the three Fab binding sites on each icosahedral asymmetric unit. | ||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6CO8 |