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8UUQ

Structure of the Measles virus Fusion protein in the pre-fusion conformation with bound [FIP-HRC]2-PEG11

Summary for 8UUQ
Entry DOI10.2210/pdb8uuq/pdb
EMDB information42595
Related PRD IDPRD_002539
DescriptorFusion glycoprotein F0, [FIP-HRC]2-PEG11, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
Functional Keywordsviral protein, glycoprotein, immune system, measles, high-resolution, ectodomain, post-fusion, small molecule, inhibitor, complex
Biological sourceMeasles virus strain Ichinose-B95a
More
Total number of polymer chains9
Total formula weight178534.84
Authors
Zyla, D.,Saphire, E.O. (deposition date: 2023-11-01, release date: 2024-07-03, Last modification date: 2024-11-13)
Primary citationZyla, 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: 38935733
DOI: 10.1126/science.adm8693
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.34 Å)
Structure validation

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PDB entries from 2024-11-20

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