Biophysical Society of Canada (BSC)
Société de Biophysique du Canada (SBC)
Peter OTTENSMEYER
University of Toronto
Images of the Invisibly Small: from Atoms to Biomacromolecular Structure and Function
In the last four decades developments in instrumentation in electron microscopy, in techniques and in specimen preparation have made it possible to image proteins such as the insulin receptor, nucleic acids, peptides such as vasopressin, and even individual atoms such as palladium, iodine and sulphur. While some of the images of these small things are spectacular, and even beautiful, it is another challenge to derive the 3D structure of biomacromolecules and their complexes from such 2D representations of reality. Over the years a number of image processing approaches for 3D reconstruction were developed, and are still being improved, for structures with high internal symmetry, or lateral 2D symmetry, or one or a few highly preferred orientations, or for structures that were completely randomly oriented when imaged. In some instances the images were sufficient to derive atomic coordinates, such as for bacteriorhodopsin; but such resolution detail has not been achieved in general. Nevertheless, even at lower resolution, the structures derived serve as crucially important 3D templates of the complexes into which to fit smaller component domains for which the structures have been solved by x-ray crystallography or NMR. While such a construct is still a static entity, for some the structure itself has lead to an understanding of their function, and of the chemistry and the mechanics by which that function is carried out. From initial microscopy to the final 3D mechanism, this process of discovery is driven by images, and so is accessible and understandable in principle by all.