+Search query
-Structure paper
Title | A neutralizing antibody prevents postfusion transition of measles virus fusion protein. |
---|---|
Journal, issue, pages | Science, Vol. 384, Issue 6703, Page eadm8693, Year 2024 |
Publish date | Jun 28, 2024 |
Authors | 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 Abstract | 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. |
External links | Science / PubMed:38935733 |
Methods | EM (single particle) |
Resolution | 2.11 - 3.6 Å |
Structure data | EMDB-42527, PDB-8ut2: EMDB-42539, PDB-8utf: EMDB-42593, PDB-8uup: EMDB-42595, PDB-8uuq: EMDB-43827, PDB-9at8: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
|
Keywords | VIRAL PROTEIN / glycoprotein / immune system / antibody / measles / high-resolution / antibody fragment / fab / neutralizing antibody / ectodomain / post-fusion / pre-fusion / small molecule / inhibitor / complex |