NMR, crystallography, and electron microscopy of nucleoprotein complexes

Abstract

The forte of electron microscopy in biology is its unique ability to elucidate the very diverse structures of biological specimens at a range of sizes, with relationships within tissue sections, between and within cells, subcellular organelles, and macromolecules, for the latter with increasingly finer detail. It is the relationship between molecules that is the essence of biology, and it is here that a major emphasis in effort has been placed in recent years in terms of structure determination, not only in electron microscopy, but also in fields with complementary structural approaches, such as the classical x-ray crystallography and the much more recent NMR spectroscopy. The spatial relationship between nucleic acids and proteins is only one facet of this effort, albeit a most important one.Conventionally electron microscopy has a spatial resolution of about 20 Å in stained biological specimens, but has succeeded with near-atomic resolutions in several cases. NMR spectroscopy per force has to start at atomic dimensions, since its inter-nuclear signals are only available at short range. It builds outward mathematically to molecular dimensions. In the process the technique has permitted the elucidation of detailed interactions, not only between atoms on the same molecule, but in a number of instances between atoms of interacting macromolecules.