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Virus crystallography and structural virology: a personal perspective

Published on Jan 2, 2015in Crystallography Reviews2.667
· DOI :10.1080/0889311X.2014.957282
Michael G. Rossmann109
Estimated H-index: 109
(Purdue University)
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 cryo-electron microscopy. This provided the basis for the investigation of lipid-enveloped viruses such as Sindbis virus and deng...
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References178
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We report on a conformational transition of dengue virus when changing the temperature from that present in its mosquito vectors to that of its human host. Using cryoelectron microscopy, we show that although the virus has a smooth surface, a diameter of ∼500 A, and little exposed membrane at room temperature, the virions have a bumpy appearance with a diameter of ∼550 A and some exposed membrane at 37 °C. The bumpy structure at 37 °C was found to be similar to the previously predicted structure...
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Many pleomorphic, lipid-enveloped viruses encode matrix proteins that direct their assembly and budding, but the mechanism of this process is unclear. We have combined X-ray crystallography and cryoelectron tomography to show that the matrix protein of Newcastle disease virus, a paramyxovirus and relative of measles virus, forms dimers that assemble into pseudotetrameric arrays that generate the membrane curvature necessary for virus budding. We show that the glycoproteins are anchored in the ga...
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