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Classification of macromolecular assemblies studied as ‘single particles’

  • Joachim Frank (a1)

In order to study proteins that do not occur in two- or three-dimensionally ordered form, one may take two different approaches: either search for conditions that induce the formation of crystals, and proceed with the established methods of X-ray or electron crystallography, or attempt to study the molecules in the form of single particles with the EM. Although many proteins have been successfully crystallized, and some general recipes for inducing ordered arrangement have been found (Mannella, 1984; Uzgiris & Kornberg, 1983), there exists a large number of proteins and protein assemblies that have resisted such attempts for a long time. Furthermore, there are macromolecular assemblies, associated with membranes and engaged in switching or gating, whose function is tied to their occurrence in isolated form, and hence are best studied without extraction from the membrane. For these reasons, the single-particle approach to the study of macromolecular structure (Frank et al. 1978, 1981; Radermacher et al. 1987a, b; for recent reviews, see Frank et al. 1985, 1988e; Frank, 1989) has found numerous applications after initial technical and conceptual hurdles were overcome. Although atomic resolution cannot be achieved with this approach for a variety of reasons, a quantitative description of architecture on the quaternary level is nevertheless possible, as exemplified in the 3D studies of ribosomal particles (overviews, see Frank et al. 1988a) and, most recently, the junctional channel complex (Wagenknecht et al. 1989a).

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