8XO2

Crystal structure of measles virus fusion inhibitor M1 complexed with F protein HR1 (HR1-42) (P21212 space group)

8XO2 の概要

• エントリーDOI: 10.2210/pdb8xo2/pdb
• 関連するPDBエントリー: 8XNE
• 分子名称: Fusion glycoprotein F1, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: fusion protein, fusion inhibitor, six-helix bundle, antiviral protein
• 由来する生物種: Measles virus strain Edmonston; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 25502.43

構造登録者

Oishi, S.,Takahara, A.,Nakatsu, T. (登録日: 2023-12-31, 公開日: 2025-01-01, 最終更新日: 2025-03-05)

主引用文献

Takahara, A.,Nakatsu, T.,Hirata, K.,Hayashi, H.,Kawaji, K.,Aoki, K.,Inuki, S.,Ohno, H.,Kato, H.,Kodama, E.,Oishi, S.
Elucidation of Postfusion Structures of the Measles Virus F Protein for the Structure-Based Design of Fusion Inhibitors.
J.Med.Chem., 68:3123-3133, 2025

PubMed Abstract: Measles is a highly infectious disease and remains a major cause of childhood mortality worldwide. In some cases, the measles virus (MV) induces subacute sclerosing panencephalitis within several years of the acute infection. The infection of the target cells by MV is mediated by the F protein, in which two heptad repeat regions, HR1 and HR2, form a six-helix bundle before membrane fusion. We previously reported anti-MV peptides, which were designed from the HR region of the MV F protein. Here, we characterized the essential interactions between the HR1 and HR2 regions on the postfusion six-helix bundles of synthetic HR1 and HR2 peptides by crystallographic studies. Based on the crystal structures, we identified the minimal α-helix sequence for antiviral activity. Additionally, optimizing HR2 peptides by introducing α-helix-inducible motifs and maintaining key hydrogen bond networks at the N- and C-terminal regions led to the identification of highly potent antiviral peptides.

PubMed: 39887040
DOI: 10.1021/acs.jmedchem.4c02337

実験手法

X-RAY DIFFRACTION (1.306 Å)