Details

Autor(en) / Beteiligte

• Delgado-Cunningham, Kevin
• López, Tomás
• Khatib, Firas
• Arias, Carlos F.
• DuBois, Rebecca M.

Titel

Structure of the divergent human astrovirus MLB capsid spike

Ist Teil von

• Structure (London), 2022-12, Vol.30 (12), p.1573-1581.e3

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Despite their worldwide prevalence and association with human disease, the molecular bases of human astrovirus (HAstV) infection and evolution remain poorly characterized. Here, we report the structure of the capsid protein spike of the divergent HAstV MLB clade (HAstV MLB). While the structure shares a similar folding topology with that of classical-clade HAstV spikes, it is otherwise strikingly different. We find no evidence of a conserved receptor-binding site between the MLB and classical HAstV spikes, suggesting that MLB and classical HAstVs utilize different receptors for host-cell attachment. We provide evidence for this hypothesis using a novel HAstV infection competition assay. Comparisons of the HAstV MLB spike structure with structures predicted from its sequence reveal poor matches, but template-based predictions were surprisingly accurate relative to machine-learning-based predictions. Our data provide a foundation for understanding the mechanisms of infection by diverse HAstVs and can support structure determination in similarly unstudied systems. [Display omitted] •Crystal structure of the human astrovirus MLB capsid spike domain is reported•Classical and MLB human astroviruses have structurally divergent capsid spikes•Competition data support the existence of multiple human astrovirus receptors•The MLB spike was a challenging target for structure prediction Delgado-Cunningham et al. report the structure of the capsid spike from human astrovirus strain MLB1. The capsid spike forms protrusions on the surface of the virus and may have a role in attaching to human cells. The MLB1 spike structure has many differences compared with classical human astrovirus spike structures.