Back

Structural determinants of rotavirus proteolytic activation

Asensio-Cob, D.; Mata, C. P.; Gomez-Blanco, J.; Vargas, J.; Rodriguez, J. M.; Luque, D.

2025-03-24 microbiology
10.1101/2025.03.24.644915 bioRxiv
Show abstract

The infectivity of rotavirus (RV), the leading cause of childhood diarrhea, hinges on the activation of viral particles through the proteolysis of the spike protein by trypsin-like proteases in the host intestinal lumen. Despite comprehensive structural characterization of the virus particle, the structural rationale behind the necessity of trypsin digestion of the VP4 protein for infectivity remains poorly understood. In this study, using cryo-electron microscopy (cryo-EM) and advanced image processing techniques, we compared uncleaved and cleaved RV virions and found that the conformation of the non-proteolyzed spike is constrained by the position of loops that surround its structure, linking the lectin domains of the spike head to its body. The proteolysis of these loops removes this structural constraint, thereby enabling the spike to undergo the necessary conformational changes required for cell membrane penetration. Thus, these loops function as regulatory elements to ensure that the spike protein is activated precisely when and where it is needed to facilitate a successful infection.

Published in PLOS Pathogens (predicted rank #2) · training set

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.