Structural determinants of rotavirus proteolytic activation.
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. In order to determine the structural basis of trypsin activation, we have used...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-08-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013063 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849228217606471680 |
|---|---|
| author | Dunia Asensio-Cob Carlos P Mata Josue Gomez-Blanco Javier Vargas Javier M Rodriguez Daniel Luque |
| author_facet | Dunia Asensio-Cob Carlos P Mata Josue Gomez-Blanco Javier Vargas Javier M Rodriguez Daniel Luque |
| author_sort | Dunia Asensio-Cob |
| collection | DOAJ |
| description | 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. In order to determine the structural basis of trypsin activation, we have used cryogenic electron microscopy (cryo-EM) and advanced image processing methods to compare uncleaved and cleaved RV particles. We find 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. |
| format | Article |
| id | doaj-art-47a657808e604befaf45f3d8a971f1d8 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-47a657808e604befaf45f3d8a971f1d82025-08-23T05:31:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-08-01218e101306310.1371/journal.ppat.1013063Structural determinants of rotavirus proteolytic activation.Dunia Asensio-CobCarlos P MataJosue Gomez-BlancoJavier VargasJavier M RodriguezDaniel LuqueThe 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. In order to determine the structural basis of trypsin activation, we have used cryogenic electron microscopy (cryo-EM) and advanced image processing methods to compare uncleaved and cleaved RV particles. We find 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.https://doi.org/10.1371/journal.ppat.1013063 |
| spellingShingle | Dunia Asensio-Cob Carlos P Mata Josue Gomez-Blanco Javier Vargas Javier M Rodriguez Daniel Luque Structural determinants of rotavirus proteolytic activation. PLoS Pathogens |
| title | Structural determinants of rotavirus proteolytic activation. |
| title_full | Structural determinants of rotavirus proteolytic activation. |
| title_fullStr | Structural determinants of rotavirus proteolytic activation. |
| title_full_unstemmed | Structural determinants of rotavirus proteolytic activation. |
| title_short | Structural determinants of rotavirus proteolytic activation. |
| title_sort | structural determinants of rotavirus proteolytic activation |
| url | https://doi.org/10.1371/journal.ppat.1013063 |
| work_keys_str_mv | AT duniaasensiocob structuraldeterminantsofrotavirusproteolyticactivation AT carlospmata structuraldeterminantsofrotavirusproteolyticactivation AT josuegomezblanco structuraldeterminantsofrotavirusproteolyticactivation AT javiervargas structuraldeterminantsofrotavirusproteolyticactivation AT javiermrodriguez structuraldeterminantsofrotavirusproteolyticactivation AT danielluque structuraldeterminantsofrotavirusproteolyticactivation |