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TitleStructural determinants of rotavirus proteolytic activation.
Journal, issue, pagesPLoS Pathog, Vol. 21, Issue 8, Page e1013063, Year 2025
Publish dateAug 12, 2025
AuthorsDunia Asensio-Cob / Carlos P Mata / Josue Gomez-Blanco / Javier Vargas / Javier M Rodriguez / Daniel Luque /
PubMed AbstractThe 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 ...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.
External linksPLoS Pathog / PubMed:40794814 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 4.4 Å
Structure data

16954

8olb

EMDB-16954, PDB-8olb:
SA11 Rotavirus Non-tripsinized Triple Layered Particle
Method: EM (single particle) / Resolution: 3.4 Å

16955

8olc

EMDB-16955, PDB-8olc:
SA11 Rotavirus Trypsinized Triple Layered Particle
Method: EM (single particle) / Resolution: 3.48 Å

16956

8ole

EMDB-16956, PDB-8ole:
Cryo-EM reconstruction of VP4 assembly from SA11 Rotavirus Non-Tripsinized Triple Layered Particle
Method: EM (single particle) / Resolution: 4.4 Å

18655

8qtz

EMDB-18655, PDB-8qtz:
Cryo-EM reconstruction of VP5*/VP8* assembly from SA11 Rotavirus Tripsinized Triple Layered Particle
Method: EM (single particle) / Resolution: 4.27 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-ZN:
Unknown entry

Source
  • rotavirus
KeywordsVIRUS / Rotavirus / dsRNA virus

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