From high symmetry to high resolution in biological electron microscopy: a commentary on Crowther (1971) ‘Procedures for three-dimensional reconstruction of spherical viruses by Fourier synthesis from electron micrographs’

Peter B. Rosenthal⇑Division of Physical Biochemistry, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UKe-mail: peter.rosenthal{at}nimr.mrc.ac.uk; peter.rosenthal{at}crick.ac.ukAbstract Elucidation of the structure of biological macromolecules and larger assemblies has been essential to understanding the roles they play in living processes. Methods for three-dimensional structure determination of biological assemblies from images recorded in the electron microscope were therefore a key development. In his paper published in Philosophical Transactions B in 1971, Crowther described new computational procedures applied to the first three-dimensional reconstruction of an icosahedral virus from images of virus particles preserved in negative stain. The method for determining the relative orientation of randomly oriented particles and combining their images for reconstruction exploited the high symmetry of the virus particle. Computational methods for image analysis have since been extended to include biological assemblies without symmetry. Further experimental advances, combined with image analysis, have led to the method of cryomicroscopy, which is now used by structural biologists to study the structure and dynamics of biological machines and assemblies in atomic detail. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. electron microscopycryomicroscopyvirusreconstructionimage analysisicosahedronFootnotesOne contribution of 18 to a theme issue ‘Celebrating 350 years of Philosophical Transactions: life sciences papers’.The featured article can be viewed at http://dx.doi.org/10.1098/rstb.1971.0054.© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.