National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
U54 AI057157
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
K08 AI103038
米国
引用
ジャーナル: Structure / 年: 2019 タイトル: Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody. 著者: Melissa Wirawan / Guntur Fibriansah / Jan K Marzinek / Xin Xiang Lim / Thiam-Seng Ng / Adelene Y L Sim / Qian Zhang / Victor A Kostyuchenko / Jian Shi / Scott A Smith / Chandra S Verma / ...著者: Melissa Wirawan / Guntur Fibriansah / Jan K Marzinek / Xin Xiang Lim / Thiam-Seng Ng / Adelene Y L Sim / Qian Zhang / Victor A Kostyuchenko / Jian Shi / Scott A Smith / Chandra S Verma / Ganesh Anand / James E Crowe / Peter J Bond / Shee-Mei Lok / 要旨: Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti- ...Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop. Here, we determined cryoelectron microscopy (cryo-EM) maps of the immDENV:anti-prM complex at different pH values, mimicking the extracellular (pH 8.0) or endosomal (pH 5.0) environments. At pH 5.0, there are two structural classes with fewer antibodies bound than at pH 8.0. These classes may represent different maturation states. Molecular simulations, together with the measured high-affinity pr:antibody interaction (versus the weak pr:E interaction) and also the low pH cryo-EM structures, suggest how antibody:pr complex can dislodge from the E protein at low pH. This exposes the E protein fusion loop enhancing virus interaction with endosomes.
全体 : Dengue virus 3 in complex with human antibody
全体
名称: Dengue virus 3 in complex with human antibody
要素
複合体: Dengue virus 3 in complex with human antibody
複合体: Fab 1H10
タンパク質・ペプチド: Fab 1H10 heavy chain (V-region)
タンパク質・ペプチド: Fab 1H10 light chain (V-region)
ウイルス: Dengue virus 3 (デング熱ウイルス)
タンパク質・ペプチド: Envelope proteinエンベロープ (ウイルス)
ウイルス: Dengue virus 3 (デング熱ウイルス)
タンパク質・ペプチド: Premembrane protein
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超分子 #1: Dengue virus 3 in complex with human antibody
超分子
名称: Dengue virus 3 in complex with human antibody / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: The virus was isolated from dengue patient. The immature dengue 3 virus was grown in Aedes Albopictus clone C6/36 cell. The anti-prM antibody 1H10 was generated from EBV-immortalized PBMC ...詳細: The virus was isolated from dengue patient. The immature dengue 3 virus was grown in Aedes Albopictus clone C6/36 cell. The anti-prM antibody 1H10 was generated from EBV-immortalized PBMC that was obtained from dengue patient.