9OC7

Crystal structure of FcRn in complex with Human Astrovirus 2 spike

9OC7 の概要

• エントリーDOI: 10.2210/pdb9oc7/pdb
• 分子名称: Spike protein VP25, IgG receptor FcRn large subunit p51, Beta-2-microglobulin (3 entities in total)
• 機能のキーワード: astrovirus, fcrn, virus host interaction, hastv, immune system
• 由来する生物種: Human astrovirus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 141753.35

構造登録者

Agrawal, S.,Wilson, I.A. (登録日: 2025-04-23, 公開日: 2025-11-19, 最終更新日: 2025-12-24)

主引用文献

Agrawal, S.,Jain, M.,Marinelli, D.,Cho, S.Y.,Briney, B.,Wilson, I.A.
Structural hijacking of FcRn by human astrovirus spikes reveals conserved epitopes for broad-spectrum antivirals.
Cell Rep, 44:116679-116679, 2025

PubMed Abstract: Human astroviruses (HAstVs) are a leading cause of pediatric gastroenteritis and emerging systemic infections; however, no targeted therapies exist. A critical barrier to intervention has been the lack of molecular insights into viral entry, particularly the interaction between the HAstV capsid spike and its receptor, the neonatal Fc receptor (FcRn). Here, we report crystal structures of the HAstV spike from classical serotypes 2 and 6 in complex with human FcRn at 3 Å resolution, defining a conserved receptor-binding interface at atomic resolution. These structures reveal serotype-specific variations that dictate receptor affinity and demonstrate that reported neutralizing antibodies can inhibit infection by sterically blocking the receptor-binding site. Mapping conserved epitopes across classical HAstV serotypes provides a blueprint for designing broad-spectrum antivirals that disrupt viral entry. Notably, our structural data rationalize the potential repurposing of clinical FcRn inhibitors, such as nipocalimab, to block HAstV infection, bridging critical gaps in astrovirus biology and antiviral development.

PubMed: 41389202
DOI: 10.1016/j.celrep.2025.116679

実験手法

X-RAY DIFFRACTION (3.07 Å)