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8UT2

Pre-fusion Measles virus fusion protein complexed with Fab 77

Summary for 8UT2
Entry DOI10.2210/pdb8ut2/pdb
EMDB information42527
DescriptorFusion glycoprotein F0, mAb 77 Light chain, mAb 77 Heavy Chain, ... (7 entities in total)
Functional Keywordsviral protein, glycoprotein, immune system, antibody, measles, high-resolution, antibody fragment, fab, neutralizing antibody, ectodomain
Biological sourceMeasles morbillivirus
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Total number of polymer chains12
Total formula weight411140.18
Authors
Zyla, D.,Saphire, E.O. (deposition date: 2023-10-30, release date: 2024-07-03, Last modification date: 2024-07-10)
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 (2.56 Å)
Structure validation

226707

数据于2024-10-30公开中

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