Virus crystallography and structural virology: a personal perspective

Abstract

My first experiences with crystallography were as a graduate student at the University of Glasgow determining the structure of aromatic hydrocarbons using only primitive hand calculation techniques. I had my first experience using electronic computers as a post-doc in the lab of William Lipscomb in Minnesota. That gave me a good preparation for the structure determination of haemoglobin with Max Perutz in Cambridge. The discovery of the conserved globin fold had a major impact on my subsequent activities. It also provided the foundation for the development of the molecular replacement method and non-crystallographic symmetry electron density averaging that was essential for the structure determination of simple icosahedral viruses. The structure determination of a common cold virus was also a major stimulus for the study of more complex viruses and the development of the use of cryoelectron microscopy. This provided the basis for the investigation of lipid-enveloped viruses such as Sindbis virus and dengue virus. It also provided the technology for the study of bacteriophage DNA packaging motors and the mechanisms of infection by tailed and untailed phages. Downloaded by [University of Connecticut] at 02:51 03 February 2015 58 M.G. Rossmann The beginnings of protein crystallographyThe most common types of crystals encountered in daily life are primarily inorganic substances such as common salt and minerals. Thus, it is not surprising that these substances were the first to be analysed in the first decade or two after the discovery of X-ray diffraction in 1912 by P. Ewald and M. von Laue in Germany and by W.H. Bragg and W.L. Bragg in England. This was most fortunate because many of these structures could be described in terms of a few atoms sitting at special positions on symmetry axes. Even so, it took a great deal of ingenuity and talent to solve these early structures as represented dramatically in the writings of C.P. Snow.[1] Gradually, with increasing experience, crystalized organic substances became within technical range. Kathleen Lonsdale, working in London, determined the structure of some benzene derivatives in 1929 and verified what chemists had suspected, that a benzene ring is planar.[2] The complexity of structures being determined increased steadily. This was aided by the introduction of Fourier syntheses by W.L. Bragg,[3] of the heavy-atom method by J.M. Robertson [4,5] and by the F 2 function by A.L. Patterson.[6] Initially, most organic structures were limited to the analysis of only the principal projections because of the large and tedious experimental procedures and the large computational tasks. Various time-saving devices had been introduced both for collecting data, such as the Weissenbeg camera, and for the computational tasks, such as Beevers-Lipson strips.[7] The power of crystallography was being demonstrated more and more in the 1930s by, for instance, J. Desmond Bernal, Dorothy Crowfoot Hodgkin and Isidor Fankuchen [8] in their work on steroids and by Dorothy Crowfoot Hodgkin in the ...

New developments in crystallography: exploring its technology, methods and scope in the molecular biosciences

“…All research results are published with no restriction [ 67 ]. There are also long traditions in the biological crystallography field of the studies of viruses on the one hand [ 68 , 69 ] and tropical diseases on the other [ 70 ]. A highly notable project is the structural genomics study of the MTb genome and its protein crystal structures ( http://webtb.org/ ).…”

A guide to the crystallographic analysis of icosahedral viruses

“…His principal interests are the study of enzyme and immunoglobulin structure, and the structures of viruses using the techniques of X-ray crystallography and atomic force microscopy. 45 Step bunches, 16 Step edge movement, 20 Step edges, 15 …”