Three-dimensional electron microscopy of biological macromolecules

The problem is treated of reconstructing the spatial structure of biological macromolecules and their aggregates (e.g., in viruses and crystals) from electron micrographs, which are two-dimensional projections of these three-dimensional objects. Potentialities of the physical methods (optical diffraction, filtering, and holography) in interpreting electron micrographs are described. The fundamentals are given of the mathematical theory of three-dimensional reconstruction from projections: the Fourier method, the algebraic methods, and the analytical methods. Applications are reviewed of the three-dimensional reconstruction methods in studying a number of objects: protein crystals, helical structures made of globular proteins, bacteriophages, and spherical viruses.