Viral coat

The jelly roll barrel is thus conceptually simple, but it can be quite puzzling if it is not considered in this way. Discussion of these structures will be exemplified in this chapter by hemagglutinin and in Chapter 16 by viral coat proteins. 

Very few self-sufficient viruses have only 60 protein chains in their shells. The satellite viruses do not themselves encode all of the functions required for their replication and are therefore not self-sufficient. The first satellite virus to be discovered, satellite tobacco necrosis virus, which is also one of the smallest known with a diameter of 180 A, has a protein shell of 60 subunits. This virus cannot replicate on its own inside a tobacco cell but needs a helper virus, tobacco necrosis virus, to supply the functions it does not encode. The RNA genome of the satellite virus has only 1120 nucleotides, which code for the viral coat protein of 195 amino acids but no other protein. With this minimal genome the satellite viruses are obligate parasites of the viruses that parasitize cells. 

The asymmetric unit contains one copy each of the subunits VPl, VP2, VP3, and VP4. VP4 is buried inside the shell and does not reach the surface. The arrangement of VPl, VP2, and VP3 on the surface of the capsid is shown in Figure 16.12a. These three different polypeptide chains build up the virus shell in a way that is analogous to that of the three different conformations A, C, and B of the same polypeptide chain in tomato bushy stunt virus. The viral coat assembles from 12 compact aggregates, or pen tamers, which contain five of each of the coat proteins. The contours of the outward-facing surfaces of the subunits give to each pentamer the shape of a molecular mountain the VPl subunits, which correspond to the A subunits in T = 3 plant viruses, cluster at the peak of the mountain VP2 and VP3 alternate around the foot and VP4 provides the foundation. The amino termini of the five VP3 subunits of the pentamer intertwine around the fivefold axis in the interior of the virion to form a p stmcture that stabilizes the pentamer and in addition interacts with VP4. 

In all jelly roll barrels the polypeptide chain enters and leaves the barrel at the same end, the base of the barrel. In the viral coat proteins a fairly large number of amino acids at the termini of the polypeptide chain usually lie outside the actual barrel structure. These regions vary considerably both in size and conformation between different coat proteins. In addition, there are three loop regions at this end of the barrel that usually are quite long and that also show considerable variation in size in the plant viruses and the... 

Figure 16.14 Schematic diagrams of three different viral coat proteins, viewed in approximately the same direction. Beta strands I through 8 form the common jelly roll barrel core, (a) Satellite tobacco necrosis virus coat protein, (b) Subunit VPl from poliovirus.

The cleft where this drug binds is inside the jelly roll barrel of subunit VPl. Most spherical viruses of known structure have the tip of one type of subunit close to the fivefold symmetry axes (Figure 16.15a). In all the picor-naviruses this position is, as we have described, occupied by the VPl subunit. Two of the four loop regions at the tip are considerably longer in VPl than in the other viral coat proteins. These long loops at the tips of VPl subunits protrude from the surface of the virus shell around its 12 fivefold axes (Figure 16.15b). 

Models also can assist in experimental design and the determination of the limits of experimental systems. For example, it is known that three proteins mediate the interaction of HIV with cells namely, the chemokine receptor CCR5, the cellular protein CD4, and the viral coat protein gpl20. An extremely useful experimental system to study this interaction is one in which radioactive CD4, prebound to soluble gpl20, is allowed to bind to cellular receptor CCR5. This system can be used to screen for... 

Assuming that all interactions of the species are possible, the system consists of the receptor CCR5 [R], radioligand CD4 [CD]), viral coat protein gpl20 [gp], and potential displacing ligand [B] ... 

Variance ratio, 239 Venn diagram, 177, 192f Viral coat protein, 44, 53 Volume of distribution, 165, 168... 

A particle that spontaneously assembles from viral coat proteins in the absence of other viral components. Vims-like particles (VLPs) generated from recombinant coat proteins are used in vaccines against hepatitis B vims and papillomavirus. 

The use of pairs of matched spectral variants of GFP, like cyan and yellow or GFP and mRed, to differentially tag proteins and look for interactions, is now in routine use. The approach can be readily applied to homodimerization of molecules that differ only by their living color or epitope tag. For example, homomultimer-ization of a viral coat protein can be observed by imaging a mixture of cyan and yellow tagged homomeric molecules [46], whereas oc-synuclein stacking can be detected by utilizing a-synuclein transcripts that encoded different epitope tags for detection by immunostaining [47],... 

Synthetic haptens mimicking some critical epitopic structures on larger macromolecules are often conjugated to carriers to create an immune response to the larger parent molecule. For instance, short peptide segments can be synthesized from the known sequence of a viral coat protein and coupled to a carrier to induce immunogenicity toward the native virus. This type of synthetic approach to immunogen production has become the basis of much of the current research into the creation of vaccines. 

In the second research strategy, plant viruses have been utilized as pliable genetic platforms for protein expression. Three formats have been developed, and the one that has undergone the most extensive evaluation is the display of epitopes on the surface of the virus as fusions with the viral coat protein. This epitope-display system... 

Some attempts have been made to rationally increase the efficiency of endosomal escape. One such avenue entails the incorporation of selected hydrophobic (viral) peptides into the gene delivery systems. Many viruses naturally enter animal cells via receptor-mediated endocytosis. These viruses have evolved efficient means of endosomal escape, usually relying upon membrane-disrupting peptides derived from the viral coat proteins. 

Viral coat proteins, see Southern bean mosaic virus, Tobacco mosaic virus, or Tomato bushy stunt virus... 

Redox Fe-S proteins High-potential iron protein Ferredoxin Viral coat proteins f Tomato bushy stunt virus protein I Southern bean mosaic virus protein Tobacco mosaic virus protein... 

The first step during a viral infection is the entry of a virus into the host cell. Viral entry is triggered by specific interactions between viral coat or envelope... 

Amantadine (C) specifically affects the replication of influenza A (RNA) viruses, the causative agent of true influenza. These viruses are endocytosed into the cell. Release of viral DNA requires protons from the acidic content of endosomes to penetrate the virus. Presumably, amantadine blocks a channel protein in the viral coat that permits influx of protons thus, uncoating is prevented. Moreover, amantadine inhibits viral maturation. The drug is also used prophylactically and, if possible, must be taken before the outoreak of symptoms. It also is an antiparkinsonian... 

Heparin has been found to bind a large number of proteins (Table 3). The biological activity of heparin and related polysaccharides is usually ascribed to their interaction with heparin-binding proteins. These proteins can be classified into classes including (1) enzymes, (2) protease inhibitors, (3) lipoproteins, (4) growth factors, (5) chemokines, (6) selectins, (7) extracellular matrix proteins, (8) receptor proteins, (9) viral coat proteins, (10) nuclear proteins, and (11) other proteins (1). Many heparin-binding proteins are enzymes and enzyme inhibitors. For example, proteases in the coagulation cascade, such as factors Ha, IXa, Xa, Xlla, and Villa, are heparin-... 

Inhibitors of the HIV protease are useful in antiviral therapy strategies because this enzyme is absolutely required for processing of proteins needed for synthesis of the viral coat. 

The 3 cylinder is a complicated structure that lies on the inside of the viral coat (Figure lc). There is one P cylinder at each icosahedral five-fold axis. The P cylinder is formed by winding the five-fold related VP3 N-termini around the symmetry axis. In close association with this cylinder is the N-terminal regions of VP1 and VP4. 

Proteins derived from viral coats are as effective in priming an immune system as is the killed virus more traditionally used for vaccines, and are safer first developed was the vaccine for hepatitis B. 

Insoluble Surface receptors (e.g., insulin receptor), antigens (e.g., viral coat proteins)... 

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