The use of EM and image analysis techniques, particularly the single particle methodology, has opened the door to the structural characterization of large protein complexes in the megadalton range. This review covers the basic principles of single particle EM and recent examples of its application to the study of large molecular machines in the eukaryotic cell. These examples will give the reader a perspective on how this emerging technique can be applied to the study of large protein complexes to determine their overall shape, or the location of subunits and domains within them, and to follow conformational changes accompanying intermediates in their functional cycle.

We are entering a new and exciting time in biology. The advent of full genome information for several organisms, including humans, provides a new tool to probe cellular structure and function. Structural genomics is now...

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