8UFO

Crystal Structure of Gastrointestinal HAstV VA1 capsid spike domain at 1.46 A resolution

8UFO の概要

• エントリーDOI: 10.2210/pdb8ufo/pdb
• 分子名称: Capsid polyprotein VP90 (2 entities in total)
• 機能のキーワード: human astrovirus, capsid spike domain, antigenicity, viral protein
• 由来する生物種: Astrovirus VA1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64466.60

構造登録者

Ghosh, A.,DuBois, R.M. (登録日: 2023-10-04, 公開日: 2024-02-14, 最終更新日: 2024-03-13)

主引用文献

Ghosh, A.,Delgado-Cunningham, K.,Lopez, T.,Green, K.,Arias, C.F.,DuBois, R.M.
Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.
Plos Pathog., 20:e1012028-e1012028, 2024

PubMed Abstract: Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.

PubMed: 38416796
DOI: 10.1371/journal.ppat.1012028

実験手法

X-RAY DIFFRACTION (1.46 Å)