8UUQ

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

8UUQ の概要

• エントリーDOI: 10.2210/pdb8uuq/pdb
• EMDBエントリー: 42595
• 関連するBIRD辞書のPRD_ID: PRD_002539
• 分子名称: Fusion 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)
• 機能のキーワード: viral protein, glycoprotein, immune system, measles, high-resolution, ectodomain, post-fusion, small molecule, inhibitor, complex
• 由来する生物種: Measles virus strain Ichinose-B95a; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 178534.84

構造登録者

Zyla, D.,Saphire, E.O. (登録日: 2023-11-01, 公開日: 2024-07-03, 最終更新日: 2024-11-13)

主引用文献

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

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

実験手法

ELECTRON MICROSCOPY (2.34 Å)