Hidden symmetry of the flavivirus protein shell and pH-controlled reconstruction of the viral surface

Biomater Sci. 2022 Dec 20;11(1):225-234. doi: 10.1039/d2bm01562e.

Abstract

Using recent Zika virus structural data we reveal a hidden symmetry of protein order in immature and mature flavivirus shells, violating the Caspar-Klug paradigmatic model of capsid structures. We show that proteins of the outer immature shell layer exhibit trihexagonal tiling, while proteins from inner and outer layers conjointly form a double-shelled close-packed structure, based on a common triangular spherical lattice. Within the proposed structural model, we furthermore rationalize the structural organization of misassembled non-infectious subviral particles that have no inner capsid. We consider a pH-controlled structural reconstruction of the outer shell from the trimeric to the dimeric state, and demonstrate that this transition, occurring during the virus maturation, can be induced by changes in protein charges at lower pH, leading to a decrease in the electrostatic interaction free energy. This transition could also be assisted by electrostatic attraction of shell proteins to the interposed lipid membrane substrate separating the shells.

MeSH terms

  • Capsid / chemistry
  • Capsid Proteins / chemistry
  • Flavivirus* / chemistry
  • Hydrogen-Ion Concentration
  • Viral Proteins* / chemistry
  • Zika Virus* / chemistry

Substances

  • Capsid Proteins
  • Viral Proteins