National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS105699
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS091263
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI176833
米国
引用
ジャーナル: Science / 年: 2024 タイトル: A neutralizing antibody prevents postfusion transition of measles virus fusion protein. 著者: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben ...著者: Dawid S Zyla / Roberta Della Marca / Gele Niemeyer / Gillian Zipursky / Kyle Stearns / Cameron Leedale / Elizabeth B Sobolik / Heather M Callaway / Chitra Hariharan / Weiwei Peng / Diptiben Parekh / Tara C Marcink / Ruben Diaz Avalos / Branka Horvat / Cyrille Mathieu / Joost Snijder / Alexander L Greninger / Kathryn M Hastie / Stefan Niewiesk / Anne Moscona / Matteo Porotto / Erica Ollmann Saphire / 要旨: Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be ...Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.
全体 : Structure of the Measles virus Fusion protein in the pre-fusion c...
全体
名称: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
要素
複合体: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
タンパク質・ペプチド: Fusion glycoprotein F0
タンパク質・ペプチド: Fusion glycoprotein F0
タンパク質・ペプチド: [FIP-HRC]2-PEG11
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
リガンド: water
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超分子 #1: Structure of the Measles virus Fusion protein in the pre-fusion c...
超分子
名称: Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3