Structure of viruses: a short history

Abstract

This review is a partially personal account of the discovery of virus structure and its implication for virus function. Although I have endeavored to cover all aspects of structural virology and to acknowledge relevant individuals, I know that I have favored taking examples from my own experience in telling this story. I am anxious to apologize to all those who I might have unintentionally offended by omitting their work. The first knowledge of virus structure was a result of Stanley's studies of tobacco mosaic virus (TMV) and the subsequent X-ray fiber diffraction analysis by Bernal and Fankuchen in the 1930s. At about the same time it became apparent that crystals of small RNA plant and animal viruses could diffract X-rays, demonstrating that viruses must have distinct and unique structures. More advances were made in the 1950s with the realization by Watson and Crick that viruses might have icosahedral symmetry. With the improvement of experimental and computational techniques in the 1970s, it became possible to determine the three-dimensional, near-atomic resolution structures of some small icosahedral plant and animal RNA viruses. It was a great surprise that the protecting capsids of the first virus structures to be determined had the same architecture. The capsid proteins of these viruses all had a 'jelly-roll' fold and, furthermore, the organization of the capsid protein in the virus were similar, suggesting a common ancestral virus from which many of today's viruses have evolved. By this time a more detailed structure of TMV had also been established, but both the architecture and capsid protein fold were quite different to that of the icosahedral viruses. The small icosahedral RNA virus structures were also informative of how and where cellular receptors, anti-viral compounds, and neutralizing antibodies bound to these viruses. However, larger lipid membrane enveloped viruses did not form sufficiently ordered crystals to obtain good X-ray diffraction. Starting in the 1990s, these enveloped viruses were studied by combining cryo-electron microscopy of the whole virus with X-ray crystallography of their protein components. These structures gave information on virus assembly, virus neutralization by antibodies, and virus fusion with and entry into the host cell. The same techniques were also employed in the study of complex bacteriophages that were too large to crystallize. Nevertheless, there still remained many pleomorphic, highly pathogenic viruses that lacked the icosahedral symmetry and homogeneity that had made the earlier structural investigations possible. Currently some of these viruses are starting to be studied by combining X-ray crystallography with cryo-electron tomography.

Revealing the Mechanisms of Protein Disorder and N-Glycosylation in CD44-Hyaluronan Binding Using Molecular Simulation

“…Such high-resolution structural information is typically obtained from X-ray crystallography or NMR spectroscopy experiments, with examples being as small as a single zinc finger domain (16) and as large as ribosomes (17) and virus capsids (18). However, not all biomolecules are equally amenable to having their structures solved by these methods.…”

In vitro evolution of high-titer, virus-like vesicles containing a single structural protein

“…One or more capsid proteins encase their RNA, matrix proteins often lie between the capsid and the membrane, and one or more transmembrane glycoproteins can interact with the matrix or capsid proteins to direct efficient particle assembly (1). Once the particles are released from cells, one or more glycoproteins in the viral envelope bind cellular receptors and catalyze membrane fusion to allow the viruses to enter new cells (2).…”

Transmission electron microscopy and the molecular structure of icosahedral viruses

“…X-ray diffraction studies on tomato bushy stunt virus (TBSV) 1 crystals proved the prediction by showing diffraction patterns reflecting icosahedral symmetry [4]. Twenty years later, protein crystallography had advanced sufficiently [5] to actually show the TBSV coat protein fold at 5.5 Å, illustrating how Caspar and Klug's quasi-equivalence theory [6] is in fact fulfilled in a T = 3 particle [7]. Crystallography of TBSV also yielded the first virus structure solved at ''atomic'' (2.9 Å) resolution [8].…”