Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure

Abstract

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we use cryoelectron microscopy to determine the capsid structure of thermostable phage P74-26 to 2.8-Å resolution. We find P74-26 capsids exhibit an overall architecture very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid to expand during genome packaging, yet maintain structural stability. The P74-26 capsid has T = 7 geometry despite being twice as large as mesophilic homologs. Capsid capacity is increased with a larger, flatter major capsid protein. Given these results, we predict decreased icosahedral complexity (i.e. T ≤ 7) leads to a more stable capsid assembly.

Acid-stable capsid structure of Helicobacter pylori bacteriophage KHP30 by single-particle cryoelectron microscopy

“…Furthermore, structural comparison of the CPs between phages KHP30 and KHP40 actually indicated the structural differences in the exterior regions (Figure 6). These trimeric CPs of phages KHP30 and KHP40 are reminiscent of trimeric CPs of other phages, such as gpD in phage l (Yang et al, 2000;Lander et al, 2008), gp87 in phage P74-26 (Stone et al, 2019), Soc in phage T4 (Qin et al, 2010;Chen et al, 2017), and Dec in phage L (Newcomer et al, 2019)…”

“…For instance, the MCP subunits of HK97 are covalently bound to form topologically linked protein catenanes arranged in icosahedral symmetry (Wikoff et al, 2000). The MCP of the thermophilic phage P74-26 has a series of rings, lassos, and flaps that topologically tether subunits together to stabilize the capsid under high-temperature conditions (Stone et al, 2019). Furthermore, the MCP of Salmonella typhimurium phage P22 has an additional I domain that is involved in capsid stability and particle assembly (Hryc et al, 2017).…”

“…The other is inter-capsomere accessory proteins that are located at the interface between the capsomeres and increase the particle stability by connecting the capsomeres. The inter-capsomere accessory proteins are further divided into dimeric (e.g., Mic1_gp47 and ε15_gp10; Jin et al, 2019;Baker et al, 2013) and trimeric protein groups (l_gpD and gp87_P74-26; Yang et al, 2000;Lander et al, 2008;Stone et al, 2019). The dimeric and trimeric accessory proteins sit on the quasi-two-fold and quasi-three-fold axes formed by pentons and hexons, respectively.…”

Diverse viruses carrying genes for microbial extremotolerance in the Atacama Desert hyperarid soil

“…High abundance and diversity of viruses in an environment with reduced encounters with viable microbial hosts, suggest that some of the Atacama soil viruses may be dormant extracellular viruses (virions) waiting for the right host population to bloom, while others remain protected by residing in the host cells as proviruses (integrated into host genomes or plasmids) or pseudolysogens (as inactive virus particles in the host cytoplasm)(20,58). Virions have been shown to endure harsh environments using a variety of mechanisms such as highly stable capsid structures(59), mineralization in silica(60) and formation of virion aggregates with lipid vesicles(61). Alternatively, viruses have been shown to seek protection in their host cells and this mode of viral survival have been observed in hot hyperarid desert soils, where lysogenic and pseudolysogenic…”

MicrographCleaner: a python package for cryo-EM micrograph cleaning using deep learning

“…Nevertheless, despite these developments, conventional particle pickers are still the preferred choice in recent publications (Gilman et al, 2019;Hiraizumi et al, 2019;Jain et al, 2019;Molina et al, 2019;Stone et al, 2019;Yan et al, 2019). Although it is likely that deep learning particle pickers will become increasingly popular, they are not perfect and different situations will require different approaches, so conventional particle pickers, especially those based on templates, will probably remain popular.…”