9DBT

Crystal structure of human astrovirus 1 capsid spike bound to human neonatal Fc receptor

9DBT の概要

• エントリーDOI: 10.2210/pdb9dbt/pdb
• 分子名称: IgG receptor FcRn large subunit p51, Beta-2-microglobulin, Structural protein (3 entities in total)
• 機能のキーワード: human astrovirus, capsid, human neonatal fc receptor, viral protein, viral protein-membrane protein complex, viral protein/membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 271418.13

構造登録者

Lentz, A.,DuBois, R.M. (登録日: 2024-08-23, 公開日: 2025-09-03, 最終更新日: 2025-11-19)

主引用文献

Lentz, A.,Lanning, S.,Iranpur, K.R.,Ricemeyer, L.,Arias, C.F.,DuBois, R.M.
Structure of the human astrovirus capsid spike in complex with the neonatal Fc receptor.
Nat Commun, 16:9621-9621, 2025

PubMed Abstract: Human astroviruses (HAstVs) are a leading cause of viral gastroenteritis in children worldwide. Recently the neonatal Fc receptor (FcRn) was identified as a receptor for HAstV, however the molecular basis for the FcRn-HAstV interaction remained unclear. Here, we report the crystal structure of FcRn bound to the HAstV capsid spike domain at 3.4 angstroms resolution. We show that all classical HAstV spikes bind to FcRn and we identify three conserved HAstV spike residues that mediate binding to FcRn. Using competition binding assays, we show that the HAstV spike competes with IgG for binding to FcRn. Additionally, we demonstrate that the FcRn inhibitor, nipocalimab, and anti-HAstV neutralizing monoclonal antibodies block HAstV spike binding to FcRn, revealing their neutralization mechanisms and supporting their therapeutic potential. Overall, our findings illuminate a crucial interaction in the HAstV life cycle, which may help to inform the development of a HAstV vaccine and antibody therapies.

PubMed: 41184319
DOI: 10.1038/s41467-025-65203-2

実験手法

X-RAY DIFFRACTION (3.4 Å)