Why large icosahedral viruses need scaffolding proteins: The interplay of Gaussian curvature and disclination interactions

TL;DR

This paper combines continuum elasticity theory and minimal simulations to explain how scaffolding proteins facilitate the error-free assembly of large icosahedral viral shells, revealing the role of Gaussian curvature and disclination interactions.

Contribution

It introduces a unified theoretical and computational framework showing how templates guide the assembly of large viral capsids with icosahedral symmetry.

Findings

Templates determine capsid size and promote error-free assembly.

Disclinations form potential wells guiding icosahedral vertices.

Continuum theory matches numerical simulations perfectly.

Abstract

While small single stranded viral shells encapsidate their genome spontaneously, many large viruses, such as the Herpes virus or Infectious Bursal Disease Virus (IBDV), typically require a template, consisting of either scaffolding proteins or inner core. Despite the proliferation of large viruses in nature, the mechanisms by which hundreds or thousands of proteins assemble to form structures with icosahedral order (IO) is completely unknown. Using continuum elasticity theory, we study the growth of large viral shells (capsids) and show that a non-specific template not only selects the radius of the capsid, but leads to the error-free assembly of protein subunits into capsids with universal IO. We prove that as a spherical cap grows, there is a deep potential well at the locations of disclinations that later in the assembly process will become the vertices of an icosahedron. Furthermore, we introduce a minimal model and simulate the assembly of viral shell around a template under non-equilibrium conditions and find a perfect match between the results of continuum elasticity theory and the numerical simulations. Besides explaining available experimental results, we provide a number of new predictions. Implications for other problems in spherical crystals are also discussed.