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Updated: Nov 21, 2025

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

Published on: September 15, 2010

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Functional refolding of the penetration protein on a non-enveloped virus

Tobias Herrmann1,2, Raúl Torres3, Eric N Salgado3,4

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

Nature
|January 14, 2021
PubMed

Insights

Rotaviruses use the VP4 protein to create membrane lesions for cell entry. Structural analysis reveals VP4 rearranges to expose a

Area of Science:

  • Virology
  • Structural Biology
  • Cell Biology

Background:

  • Non-enveloped viruses require membrane disruption for cell entry.
  • Rotavirus entry into host cells is mediated by the viral protein VP4.

Purpose of the Study:

  • To elucidate the molecular mechanism by which rotavirus VP4 protein mediates membrane penetration.
  • To determine the structural rearrangements of VP4 during viral entry.

Main Methods:

  • Electron cryomicroscopy (cryo-EM) was used to determine the structure of VP4 on the rotavirus surface.
  • Electron cryotomography was employed to visualize virus particles entering cells.
  • A disulfide mutant of VP4 was utilized to stabilize intermediate conformations.

Main Results:

  • Activated VP4 (VP8* and VP5*) undergoes a conformational change from an 'upright' to a 'reversed' state on the virion surface.
  • The 'reversed' VP4 conformation exposes a buried 'foot' domain, which interacts with the host cell membrane.
  • Cryotomographic data support the proposed mechanism of VP4-mediated membrane penetration.

Conclusions:

  • The study defines the molecular mechanism of rotavirus membrane penetration, initiated by VP4 conformational changes.
  • The findings suggest VP4's mechanism of action may share similarities with other viral entry pathways.
  • This research provides critical insights into the early stages of rotavirus infection.

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