Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 174

Regardless of their size and architectural sophistication, all virions contain at least one protein coat, the capsid or nucleocapsid, which encases and protects the nucleic acid genome (Table 4.2). As first pointed out by Francis Crick and James Watson in 1956, most virus particles appear to be rod shaped or spherical under the electron microscope. Because the coding capacities of viral genomes known at that time were very limited, these authors proposed that construction of capsids from a small number of subunits would minimize the genetic cost of encoding structural proteins. Such genetic economy dictates that capsids be built from identical copies of a small number of viral proteins with properties that permit regular and repetitive interactions among them. These protein molecules are arranged to provide maximal contact and noncovalent bonding among subunits and structural units. We now know that the capsids of even the largest viruses, with genomes of >1 Mbp, are also built from a small number of proteins. This property indicates that optimization of regular protein-protein interactions is the primary determinant of virus architecture. The repetition of such interactions among a limited number of proteins results in a regular structure, with symmetry that is determined by the spatial patterns of the interactions. The helical or icosahedral symmetry common to many viruses not only satisfies such protein limitations but also has considerable practical value (Box 4.2).

Figure 4.5 Difference mapping illustrated by a 6-Å-resolution reconstruction of adenovirus. (A) Comparison of α-helices of the penton base in the cryo-electron microscopic (cryo-EM) density (gray mesh) and the crystal structure of this protein bound to a fiber peptide (ribbon). The excellent agreement established that α-helices could be reliably discerned in the 6-Å cryo-EM reconstruction. (B) Portion of the cryo-EM difference map corresponding to the surface of one icosahedral face of the capsid. The crystal structures of the penton base (yellow) and the hexons (green, cyan, blue, and magenta at different positions) at appropriate resolution were docked within the cryo-EM density at 6-Å resolution. The cryo-EM density that does not correspond to these structural units (the difference map) is shown in red. At this resolution, the difference map revealed four trimeric structures located between neighboring hexons and three bundles of coiled-coiled α-helices. Both assemblies are now known to be formed by cement protein IX. Adapted from Saban SD et al. 2006. J Virol 80:12049–12059, with permission. Courtesy of Phoebe Stewart, Vanderbilt University Medical Center.