Virus jelly roll barrels

The coat proteins of many different spherical plant and animal viruses have similar jelly roll barrel structures, indicating an evolutionary relationship... 

One of the most striking results that has emerged from the high-resolution crystallographic studies of these icosahedral viruses is that their coat proteins have the same basic core structure, that of a jelly roll barrel, which was discussed in Chapter 5. This is true of plant, insect, and mammalian viruses. In the case of the picornaviruses, VPl, VP2, and VP3 all have the same jelly roll structure as the subunits of satellite tobacco necrosis virus, tomato bushy stunt virus, and the other T = 3 plant viruses. Not every spherical virus has subunit structures of the jelly roll type. As we will see, the subunits of the RNA bacteriophage, MS2, and those of alphavirus cores have quite different structures, although they do form regular icosahedral shells. 

The canonical jelly roll barrel is schematically illustrated in Figure 16.13. Superposition of the structures of coat proteins from different viruses show that the eight p strands of the jelly roll barrel form a conserved core. This is illustrated in Figure 16.14, which shows structural diagrams of three different coat proteins. These diagrams also show that the p strands are clearly arranged in two sheets of four strands each P strands 1, 8, 3, and 6 form one sheet and strands 2, 7, 4, and 5 form the second sheet. Hydrophobic residues from these sheets pack inside the barrel. 

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). 

The biggest variations are in the loops—in size and additional secondary structural elements (or complete domains) that they contain. In the nonenveloped vertebrate viruses, it is the external loops that contain the antigenic sites (Rossmann et al, 1985 Tsao et al, 1991), with epitopes formed where several loops come together. The nomenclature BC is used to describe the loop between strands B and C. Generally, the BC, HI, DE, and EG loops that are close to the 5-fold/quasi-6-fold axes tend to be short, whereas the CD, EF, and GH loops tend to be longer. Whereas most of the jelly-roll / barrels are about 180 amino acids, they go up in size to 584 amino acids in parvoviruses with large insertions in the loops (Tsao et al, 1991). 

Figure 16.13 The known subunit structures of plant. Insect, and animal viruses are of the jelly roll antiparallel p barrel type, described in Chapter 5. This fold, which is schematically illustrated in two different ways, (a) and (b), forms the core of the S domain of the subunit of tomato bushy stunt virus (c). [(b), (c) Adapted from A.J. Olson et al., /. Mol. Biol. 171 61-93, 1983.1...

All known single positive-sense strand [(+)ssRNA] plant virus capsids are built from jelly-roll /3-barrel building blocks. They represent the most classic expression of the canonical domain form, with few of the embellishments seen in the animal virus homologs described later. Perhaps there was not the selective pressure to decorate the surface with loops of variable sequence, because immune surveillance was not as stringent as in animal hosts. The result is that the plant loops between the /3 strands are consistently shorter. 

Satellite viruses are those that are dependent for their own replication on some (catalytic) activity encoded in another helper virus that coinfects the host cell. The structures of three plant ssRNA satellite viruses represent some of the highest resolutions known and have been comparatively reviewed (Ban et al., 1995). The structures of satellite tobacco mosaic virus (STMV) (Larson et al., 1993a,b), satellite tobacco necrosis virus (STNV) (Jones and LUjas, 1984 Liljas et al., 1982), and satellite panicum mosaic virus (SPMV) (Ban and McPherson, 1995) have T=1 capsids composed of 60 identical copies of unembellished jelly-roll j3 barrels constructed of only 155 to 195 amino acids (Fig. la see Color Insert). What is remarkable is how little the assembly context of these domains is conserved. The same end always points toward the 5-fold axis, but the domains are rotated to different extents around the 5-fold axis. Furthermore, between STNV and the others, there is a 70° rotation of the barrel about its long axis. Contacts across the dimer interface are... 

The structure of human rhinovirus 16 (HRV16) was pursued at higher resolution (2.15 A) than most, and revealed interesting structures around the 5-fold axis (Hadfield et al., 1997). These were composed in part of residues that had been disordered in prior rhinoviral crystal structures, but had been seen in type 3 poliovirus (Filman et al, 1989). N termini of five symmetry-equivalent VPS come together to form a five-stranded parallel /3 barrel, plugging a gap between the five VPl jelly-roll domains. Each of 5 VP4 N termini contributes a / hairpin to a 10-stranded antiparallel /3 barrel closer to the virus center. In both rhino- and polioviruses VP4 is N-terminally myristoylated and these elements of structure are thought to be intimately involved with conformational transitions that occur on cell entry and uncoating. 

Viral capsid proteins, in E. coli, 5 Viral genome organization, 219 Viral phylogeny, 185-186 Viral protein structural folds, 125-186 determination of, 125-126 four-helix bundle, 132 immunoglobulin fold, 131 jelly-roll /3 barrel, 128-131, 129 serine protease fold, 132 terminology, 125 virus families and, 125 Viral replication cycle, 8... 

Chapman and Liljas, Fig. 1. The canonical jelly-roll fi barrel seen in many capsid structures, as exemplified by (a) satellite Panicum panicum mosaic virus (Ban and McPherson, 1995), (b) poliovirus VPS (Filman et al, 1989), (c) canine parvovirus (Filman et al., 1989), and (d) Nudaurelia capensis ui virus (Munshi et al, 1996). The view is approximately tangential to the capsid surface. As in many of the figures, the eight strands of the jelly roll are highlighted by darker colors from blue (/IB) to red (/II) The visible N termini and C termini are marked with Nt and Ct, respectively, and the loops connecting the strands are denoted BC, CD, etc. All the ribbon drawings have been made with the program Molscript (Kraulis, 1991). 

Strand which then returns via two hairpin connections to the strand adjacent to the first. This feature contains a handedness that is only observed in one sense as shown in Fig. 13a. Connection of two of these features gives rise to an eight stranded y3-barrel however, Greek Key motifs are utilized in many ways to form closed structures. An alternative way of forming a closed barrel is found in proteins that exhibit a jelly roll topology (Fig. 13b). This is an abundant motif that is commonly found in virus capsid proteins. 

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