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TitleA neutralizing antibody prevents postfusion transition of measles virus fusion protein.
Journal, issue, pagesScience, Vol. 384, Issue 6703, Page eadm8693, Year 2024
Publish dateJun 28, 2024
AuthorsDawid 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 AbstractMeasles 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 linksScience / PubMed:38935733
MethodsEM (single particle)
Resolution2.11 - 3.6 Å
Structure data

EMDB-42527, PDB-8ut2:
Pre-fusion Measles virus fusion protein complexed with Fab 77
Method: EM (single particle) / Resolution: 2.56 Å

EMDB-42539, PDB-8utf:
Structure of the Measles virus Fusion protein in the post-fusion conformation
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-42593, PDB-8uup:
Structure of the Measles virus Fusion protein in the pre-fusion conformation
Method: EM (single particle) / Resolution: 2.11 Å

EMDB-42595, PDB-8uuq:
Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11
Method: EM (single particle) / Resolution: 2.34 Å

EMDB-43827, PDB-9at8:
Fab 77-stabilized MeV F ectodomain fragment
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • mus musculus (house mouse)
  • measles morbillivirus
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / glycoprotein / immune system / antibody / measles / high-resolution / antibody fragment / fab / neutralizing antibody / ectodomain / post-fusion / pre-fusion / small molecule / inhibitor / complex

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