Viruses Self-assembly

Some viruses do not directly follow the DNA mRNA protein path. Retroviruses, for example, are composed of RNA and consequently replicate by a pathway of RNA -> DNA -> mRNA -> protein. After a retrovirus infects a cell, the viral RNA cargo is converted to DNA via the enzyme, reverse transcriptase. The viral DNA then integrates into the host cell s DNA. Expression of the viral genes by the host s transcriptional and translational machinery build the components for new viruses. Self-assembly of the components then occurs. Retroviruses are not biological curiosities they are the agents of diseases, such as human T-cell leukemia and acquired immune deficiency syndrome (AIDS). 

The HIV capsid is made up of auto-assembled protease-cleaved Gag polyprotein. This self-assembly cannot take place when appropriately positioned mutations are present, resulting in a drastically reduced infectivity of the progeny virus. Recently,... 

Such a subunit structure permits the construction of the virus partieles by a proeess in which the subunits self-assemble into structures held together by non-eovalent intermolecular forces as occurs in the process of erystallization. This eliminates the need for a sequenee of enzyme-catalysed reactions for coat synthesis. It also provides an automatic quality-control system, as subunits which may have major stmctural defects fail to become ineorporated into complete partieles. 

The non-enveloped human viruses all have icosahedral capsids. The structural proteins undergo a self-assembly process to form capsids into which the viral nucleic acid is packaged. Most non-enveloped viruses accumulate within the cytoplasm or nucleus and are only released when the cell lyses. 

Hepatitis B surface antigen Monomer has 226 amino acids Yeast Mammalian cells Vaccination Approved for sale Monomer self-assembles into structure resembling virus particles... 

In all cases, the characteristic structure of the virus is determined by the structure of the protein subunits of which it is constructed. Self-assembly leads to the final virus particle. 

Completely different mechanisms are involved in the self-assembly of the tobacco mosaic virus (TMV). This virus consists of single-strand RNA, which is surrounded by 2,130 identical protein units, each of which consists of 158 amino acid residues. A virus particle, which requires the tobacco plant as a host, has a rodlike structure with helical symmetry ( Stanley needles ). It is 300 nm long, with a diameter of 18nm. The protein and RNA fractions can be separated, and the viral... 

Examples. 2D SAXS/WAXS experiments on highly anisotropic polymer materials during melting and crystallization can be used to visualize and understand the evolution of nanostructure [56,57], Transformations of biopolymers in solution, e.g., virus crystallization can be studied in situ [58], It is possible to study solidification mechanisms of spider silk [59], or the self-assembly of micelles on a time-scale of milliseconds [60],... 

The species and properties defining a given level of complexity result from and may be explained on the basis of the species belonging to the level below and of their multibody interaction, e.g. supramolecular entities in terms of molecules, cells in terms of supramolecular entities, tissues in terms of cells, organisms in terms of tissues and so on up to the complexity of behavior of societies and ecosystems. For example, in the self-assembly of a virus shell, local information in the subunits is sufficient to tell the proteins where to bind in order to generate the final polypro-teinic association, thus going up a step in complexity from the molecular unit to the... 

In a paper describing the structure of regular viruses, Caspar and Klug [4] have shown that viral capsids use self-assembly to construct spherical shells up to a hundred nanometers in diameter by utilizing identical copies of proteins as chemical... 

Pitard B, et al. Virus-sized self-assembling lamellar complexes between plasmid DNA and cationic micelles promote gene transfer. Proc Natl Acad Sci USA 1997 94 14412. 

The transformation from spheres to cyhnders is a peculiar example for the self-adjustment of the molecular conformation. The switching shape can be regarded as an example for the principle of quasi equivalency established by A. Klug for the self-assembly of biomolecules and viruses [145] for the sake of an improved intermolecular packing, the molecules adopt a conformation different from the minimum energy one. This also demonstrates that shape control does not mean a fully constrained structure. Similar to biomolecules, the combination of flexible macromolecules and self-assembly principles is a powerful strategy for preparation of molecules with well-defined but switchable shape [23]. 

True self-assembly is observed in the formation of many oligomeric proteins. Indeed, Friedman and Beychok reviewed efforts to define the subunit assembly and reconstitution pathways in multisubunit proteins, and all of the several dozen examples cited in their review represent true self-assembly. Polymeric species are also formed by true self-assembly, and the G-actin to F-actin transition is an excellent example. By contrast, there are strong indications that ribosomal RNA species play a central role in specifying the pathway to and the structure of ribosome particles. And it is interesting to note that the assembly of the tobacco mosaic virus (TMV) appears to be a two-step hybrid mechanism the coat protein subunits first combine to form 34-subunit disks by true self-assembly from monomeric and trimeric com-... 

Dendrimers are being used as host molecules, catalysts, self-assembling nanostructures analogs of proteins, enzymes, and viruses and in analytical applications including in ion-exchange displacement chromatography and electrokinetic chromatography. 

Hewat, E. A., Booth, T. F. and Roy, R (1994). Structure of correctly self-assembled bluetongue virus-like particles. /. Struct. Biol. 112,183-191. 

Another complex macromolecular aggregate that can reassemble from its components is the bacterial ribosome. These ribosomes are composed of 55 different proteins and by 3 different RNA molecules, and if the individual components are incubated under appropriate conditions in a test tube, they spontaneously form the original structure (Alberts et al., 1989). It is also known that even certain viruses, e.g., tobacco mosaic virus, can reassemble from the components this virus consists of a single RNA molecule contained in a protein coat composed by an array of identical protein subunits. Infective virus particles can self-assemble in a test tube from the purified components. 

Nanostructures are, literally, facts of life in biology. Proteins, viruses, and bacteria are nanosized, three-dimensional structures which have been self assembled from smaller subunits. Although individual atoms in the subunits (polypeptides, for example) are covalently linked, assembly of the subunits is maintained by non-covalent (van der Waals, hydrogen-bonding, electrostatic, and hydrophobic) interactions. 

The electrostatic forces also play an important role in the conformation and structure of macromolecules such as polymers, polyelectrolytes, and proteins. The self-assembly of proteins from disks to virus is triggered by electrostatic interactions between neighboring subunits. In the case of polyelectrolytes (polymer molecules with charges) and charged colloids, transport behavior such as rheology is also affected significantly by charge effects, as we have already seen in Chapter 4. 

Because eicosahedra are regular geometric solids and the faces can be made up of hexons and pentons of identical subunits, it might seem that self-assembly of eicosahedral viruses would occur easily. However, the subunits usually must be able to assume three or more different conformations and the shells can easily be assembled incorrectly. Several stategies are em-... 

Another important application of this interaction is in the formation of self-assembled bilayers on silver or gold surfaces. Ebersole et al. [457] showed that avidin and streptavidin molecules will adsorb onto clean layers of Au or Ag from an aqueous solution. Such layers can then be employed to capture biotinylated compounds. These authors used this technique to attach fragments of nucleic acid derived from the herpes virus to a solid support. A more popular approach to this general problem has, however, been to start by adsorption of a suitable biotin... 

---