Why large icosahedral viruses need scaffolding proteins - PubMed (original) (raw)
Why large icosahedral viruses need scaffolding proteins
Siyu Li et al. Proc Natl Acad Sci U S A. 2018.
Abstract
While small single-stranded viral shells encapsidate their genome spontaneously, many large viruses, such as the herpes simplex virus or infectious bursal disease virus (IBDV), typically require a template, consisting of either scaffolding proteins or an 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 nonspecific template not only selects the radius of the capsid, but also 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 a viral shell around a template under nonequilibrium 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 predictions. Implications for other problems in spherical crystals are also discussed.
Keywords: continuum elasticity theory; scaffolding proteins; self-assembly; virus.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Fig. 1.
(A) From Left to Right: bacteriophage P22 (28), bacteriophage N4 (29), rotavirus (30), herpes simplex virus (31), phage ΦM12 (32), and pseudoalteromonas virus PM2 (33). The triangulation number of each virus is shown below it. The scaffolding proteins and hydrogenases inside the capsid of bacteriophage P22 and the inner shell of rotavirus are shown. To form structures with IO, all viruses shown need scaffolding proteins as illustrated for bacteriophage P22. Only rotavirus requires a preformed scaffolding layer. Rotavirus belongs to the Reoviridae virus family, and these viruses all form T=13 and have multishell structures. Bacteriophage P22 reprinted with permission from ref. , Springer Nature:
Nature Chemistry
, copyright (1995). Rotavirus reprinted from ref. . Copyright (2003), with permission from Elsevier. Herpes simplex virus from ref. . Reprinted with permission from
AAAS
. Pseudoalteromonas virus republished with permission of Microbiology Society, from ref. ; permission conveyed through Copyright Clearance Center, Inc. Bacteriophage N4 and phage ΦM12 are rendered in UCSF Chimera, based on Electron Microscopy Data Bank accession nos. EMD-1472 and EMD-5718. (B) Capsids obtained in the simulations from Left to Right: T=7, T=9, T=13, T=16, T=19, and T=21.
Fig. 2.
Dynamics of formation of a hexamer vs. a pentamer. Five trimers are attached at a vertex with an opening angle close to π/3 at the top and much smaller than π/3 at the bottom. If the energy per subunit of formation of a pentamer Ep is higher than that of a hexamer EH, then a hexamer forms (Top); otherwise, a pentamer assembles (Bottom).
Fig. 3.
The 1D energy plot for the first disclination. The dotted line corresponds to disclination self-energy Eself (Eq. 11), the dashed line corresponds to the Gaussian curvature–disclination interactions E0d, and the solid line is the result of the addition of both energies Fcl−E0 (Eq. 10) as a function of the location of disclination in the shell for θm=0.7. The energy goes through a minimum for r=0.66R. Inset graph shows the zoom-out energy plot where the circle region corresponds to the main graph.
Fig. 4.
The snapshots of a T = 13 growth in discrete simulation (A) and continuum theory (B). The caps in A correspond to the simulation growth with triangles representing the trimers. The yellow vertices belong to pentamers, blue ones to hexamers, and red ones to the cap edge. The gold core mimics the preformed scaffolding layer or inner core. The caps in B denote the energy contour plots for the newest disclinations that appear in the purple energy well, with geodesic shell size Rm=Rθm. The red region has the highest energy and the purple region the lowest one. There is a yellow ball in the position of each disclination. The largest ball corresponds to a newly formed disclination.
Fig. 5.
The stretching energy of a T = 13 shell as a function of the number of trimeric subunits. For small FvK numbers (γ=2, black line), there is no significant drop in energy as a pentamer forms. However, for large FvK numbers (γ≫1), the formation of pentamers drastically lowers the energy of the elastic shell.
Fig. 6.
The role of SPs in the formation of the T=13 capsid of IBDV. Without SPs, the CPs (blue and white subunits) of IBDV form a T=1 structure (Top). In the presence of SPs (yellow subunits), they form a T=13 structure (Bottom). The results of our simulations are also illustrated next to each intermediate step. Note that SPs (yellow subunits) do not assemble without the CPs but probably experience some conformational changes during the assembly. However, our focus here is solely on the impact of scaffolding on the CPs, resulting in a change in the capsid T number. For preformed SPs, as in the case of bluetongue virus, the core is spherical and there is no indication of any changes in the size of the spherical template during the assembly.
References
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