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-Structure paper
タイトル | A neutralizing antibody prevents postfusion transition of measles virus fusion protein. |
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ジャーナル・号・ページ | Science, Vol. 384, Issue 6703, Page eadm8693, Year 2024 |
掲載日 | 2024年6月28日 |
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 / |
PubMed 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. |
リンク | Science / PubMed:38935733 |
手法 | EM (単粒子) |
解像度 | 2.11 - 3.6 Å |
構造データ | EMDB-42527, PDB-8ut2: EMDB-42539, PDB-8utf: EMDB-42593, PDB-8uup: EMDB-42595, PDB-8uuq: EMDB-43827, PDB-9at8: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN / glycoprotein / immune system / antibody / measles / high-resolution / antibody fragment / fab / neutralizing antibody / ectodomain / post-fusion / pre-fusion / small molecule / inhibitor / complex |