9AT8
Fab 77-stabilized MeV F ectodomain fragment
Summary for 9AT8
Entry DOI | 10.2210/pdb9at8/pdb |
EMDB information | 43827 |
Descriptor | Fusion glycoprotein F0, mAb 77 light chain, mAB 77 heavy chain, ... (4 entities in total) |
Functional Keywords | viral protein, glycoprotein, immune system, antibody, measles, high-resolution, antibody fragment, fab, neutralizing antibody, ectodomain |
Biological source | Measles virus strain Ichinose-B95a More |
Total number of polymer chains | 4 |
Total formula weight | 193235.13 |
Authors | Zyla, D.,Saphire, E.O. (deposition date: 2024-02-26, release date: 2024-07-03, Last modification date: 2024-11-06) |
Primary citation | Zyla, D.S.,Della Marca, R.,Niemeyer, G.,Zipursky, G.,Stearns, K.,Leedale, C.,Sobolik, E.B.,Callaway, H.M.,Hariharan, C.,Peng, W.,Parekh, D.,Marcink, T.C.,Diaz Avalos, R.,Horvat, B.,Mathieu, C.,Snijder, J.,Greninger, A.L.,Hastie, K.M.,Niewiesk, S.,Moscona, A.,Porotto, M.,Ollmann Saphire, E. A neutralizing antibody prevents postfusion transition of measles virus fusion protein. Science, 384:eadm8693-eadm8693, 2024 Cited by 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 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. PubMed: 38935733DOI: 10.1126/science.adm8693 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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