Prototypical Viral Folds

In this section the folds of domains found repeatedly in different viruses are described. The discussion is of the canonical form with details of the differences between different viruses following in the survey of viral taxa. 

Domains in different viruses differ in several ways. There may be one or two additional strands. Strand A is found in some viruses, but in different locations, sometimes as a direct extension of sheet BIDG, sometimes domain swapped so that it hydrogen bonds with a neighboring subunit. Within the core barrel, strand lengths differ. For T=1 capsids /3B ranges from 9 to 17 amino acids, / C from 3 to 10, /3D from 10 to 25, and so on (Xie and Chapman, 1996). 

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). 

With few exceptions, the jelly-roU proteins forming capsids have arms at their N termini and often also at their C termini. These arms are often partly disordered, and the disordered segments might be important for interaction with the nucleic acid molecule. Ordered parts of these arms are used to regulate subunit packing and particle stability. 

The four-helix bundle is a common motif in which (usually) antiparallel a helices are packed side by side. It is found in myohemerythrin, various cytochromes, and a number of other proteins. A viral example is the coat protein of tobacco mosaic virus (TMV) (Bloomer et al, 1978). TMV represents the most common type, in which the helix axes are nearly antiparallel, off by 18°, coiled with a left-handed superhelical twist (Fig. 5 see Color Insert). The slight misalignment of the individual helix axes allows the side chains to interdigitate efficiently, burying internal hydrophobic side chains. 

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In July 2000 Bartel and coworkers published the impressive example of a single RNA sequence that can adopt either of two ribozyme (Box 22) folds and catalyze two different reactions (Figure 1.1.1) [8]. One reaction is cleavage of RNA catalyzed by the hepatitis delta vims (HDV) ribozyme, which assists the replication of HDV viral RNA. The other is RNA ligation catalyzed by the class III ligase ribozyme, an activity obtained in the laboratory in in-vitro selection experiments. The two ribozyme folds are completely different and do not have a single base pair in common. Importantly, minor variants of this sequence are highly active for one or other catalytic activity and can be accessed from the prototype by a few nucleotide mutations only. 

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