Bite the bullet
Most viruses are either helical or icosahedral in structure. The two highly symmetric shapes permit viruses to use the same component protein multiple times to create large structures from a minimum number of distinct protein species. The strategy conserves the amount of genetic material viruses need to encode structural proteins. Although the two basic shapes serve the needs of viruses more or less equally well, structural biologists have had a much easier time determining the structures of the icosahedra. For example, while more than one hundred high resolution structures of icosahedral viruses are now available, the number of comparable helical virus structures is limited to helical plant viruses such as tobacco mosaic virus and filamentous bacteriophage such as E. coli phage f1. It’s not as though helical animal and human viruses are of limited interest. Just the opposite. They include influenza virus plus members of the paramyxo-, rhabdo- bunya-, corona, filo- and arenavirus families, all of which contain important human pathogens. The problem is that structural analysis of these viruses is unusually difficult. The protein-RNA complex is often disordered or weakly ordered in the virion, and the viruses have a membrane, a structure that complicates both crystallization and electron microscopic analysis.
To advance our knowledge of helical virus structure, investigators have focused their attention on the rhabdoviruses, a family of bullet-shaped viruses that includes rabies and vesicular stomatitis viruses (VSV). Rhabdoviruses have a helical nucleocapsid that is well ordered over most of the virion length. Although a membrane is present, it is tightly wrapped around the nucleocapsid, and does not obscure the helix in electron micrographs of the virion. With such excellent images, one would think it would be a simple matter to compute a three-dimensional reconstruction of the particle. No structure has been forthcoming, however, despite the best efforts of many highly talented structural biologists – until now.
- Cryo-EM Model of the Bullet-Shaped Vesicular Stomatitis Virus. 2010 Science 327 (5966) 689-693 doi:10.1126/science.1181766
Assembly of a virus particle is generally presumed to be a stochastic process. However, assembly of VSV appears to follow a well-orchestrated program. It begins with RNA and N as a nucleocapsid ribbon. The ribbon curls into a tight ring and then is physically forced to curl into larger rings that eventually tile the helical trunk. M subunits bind on the outside of the nucleocapsid, rigidify the bullet tip and then the trunk, and create a triangularly packed platform for binding G trimers and envelope membrane, all in a coherent operation during budding.