Capsid Proteins Self-assemble to Form Stable Shell

Biological Strategy

AskNature Team

Image: NIAID / Flickr / Some rights reserved

Chemically Assemble on Demand

The vast majority of biochemical assembly and break down processes––even by the most complex organisms––occur within cells. In fact, cells are able to perform hundreds, even thousands, of chemical transformations at the same time under life-friendly conditions (ambient temperature and pressure in an aqueous environment). For example, venomous snakes store precursor molecules to instantly synthesize a suite of toxins via enzyme-mediated cascades.

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Chemically Assemble Molecular Devices

Through molecular recognition and shape complementarity, cells self-assemble complex devices that work in much the same way that human machines do, but at a molecular scale. For example, single-celled bacteria construct a “motor” responsible for the controlled motion of the bacteria’s flagellar tail.

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Physically Assemble Structure

Living systems use physical materials to create structures to serve as protection, insulation, and other purposes. These structures can be internal (within or attached to the system itself), such as cell membranes, shells, and fur. They can also be external (detached), such as nests, burrows, cocoons, or webs. Because physical materials are limited and the energy required to gather and create new structures is costly, living systems must use both conservatively. Therefore, they optimize the structures’ size, weight, and density. For example, weaver birds use two types of vegetation to create their nests: strong, a few stiff fibers and numerous thin fibers. Combined, they make a strong, yet flexible, nest. An example of an internal structure is a bird’s bone. The bone is comprised of a mineral matrix assembled to create strong cross-supports and a tubular outer surface filled with air to minimize weight.

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Capsids, the containers housing viral DNA, are stable, self-assembling structures because they rely on the net strength afforded by a combination of weak attractive or repulsive forces arising from the relative position of proteins making up the container

Viruses are essentially mobile DNA containers that implicate themselves into living cells by usurping the cell’s reproductive machinery to reproduce their own DNA. Viral DNA is housed in protective nano-scale containers, called capsids, that self-assemble within the host cell. These resilient proteinaceous packets self-assemble in response to a variety of weak forces that, in concert, provide the capsid with a great deal of stability. The weak forces at work include attraction or repulsion between electrostatic charges, water solubility, and constituent structures in various parts of the capsid.

Watch Video of Virus Self-Assembling (5:31 min)

Image: San Diego Supercomputer Center / J. Beaver / San Diego Supercomputer Center /

The image shows the MS2 bacteriophage, a virus whose genome was one of the first ever determined. Part of NIH-supported research and tool development led by Professor Philip Bourne SDSC/UCSD, the image shows the complete viral protein coat, attached to short pieces of the viral genome (14 bases out of 3,569 total). The viral coat is made up of a single protein repeated 60 times (ribbon), creating a sphere that holds only the viral genetic information (shown as spheres and cylinders) and a single protein related to maturation (not shown).

Image: nathan Andrew Baker / Flickr /

Last Updated October 13, 2016

References

“Viruses are nanosized, genome-filled protein containers with remarkable thermodynamic and mechanical properties. They form by spontaneous self-assembly inside the crowded, heterogeneous cytoplasm of infected cells. Self-assembly of viruses seems to obey the principles of thermodynamically reversible self-assembly but assembled shells (‘capsids’) strongly resist disassembly. Following assembly, some viral shells pass through a sequence of coordinated maturation steps that progressively strengthen the capsid. Viral shells have effective Young’s moduli ranging from that of polyethylene to that of plexiglas. Some of them can withstand internal osmotic pressures that are tens of atmospheres.” (Roos et al. 2010:733)

“Viruses do not carry out metabolic activity and rely entirely on host-cell molecular machinery for reproduction. This absence of metabolic and reproductive activity suggests that, unlike cells, the assembly of viruses could perhaps be understood on the basis of equilibrium thermodynamics…Capsid proteins, or ‘subunits’, interact mainly through a combination of electrostatic repulsion, hydrophobic attraction and specific contacts between certain pairs of amino acids (known as ‘Caspar pairs’)…Self-assembly of most infectious sphere-like ssRNA viruses under ambient conditions requires the presence of the viral RNA genome molecules. Viral RNA molecules act in part as a non-specific ‘electrostatic glue’ that links together the oppositely charged capsid proteins, and particular ‘stem-loop’ side branches of the RNA molecules have specific affinity for the capsid proteins…On the other hand, self-assembly of viral shells of most ds genomes, such as the tailed dsDNA ‘bacteriophage’ viruses (that is, viruses that prey on bacteria), does not require the presence of genome molecules. The much larger bending rigidity of dsDNA molecules presumably prevents them from acting as ‘electrostatic glue’. In these cases, the genome is usually inserted, after capsid assembly has been completed, by the action of a rotary molecular motor imbedded in the capsid.” (Roos et al. 2010:733-734)

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