ELECTRON MICROSCOPY IN THE CONTEXT OF STRUCTURAL SYSTEMS BIOLOGY
As modern molecular biology moves from single molecules toward more complex multi-molecular machines, the need for structural information about these assemblies grows. Nuclear magnetic resonance (NMR) spectroscopy (see Chapter 5) and X-ray crystallography (see Chapter 4) are well-established approaches for obtaining atomic structures of biological macromolecules, but it has become increasingly clear that the structures of individual components of assemblies can only be a first step to understanding a biological phenomenon.
Based on the analysis of genome sequences, it was suggested that life depends on about 200-300 core biological processes (Martin and Drubin, 2003). Each of these processes involves multiple proteins, often organized into large heterogeneous assemblies, with a wide range of morphologies and complexity. The “parts list” that has emerged from the genome project and from structural genomics is far from a “wiring diagram” that we need to understand these processes. Detailed knowledge of the parts of a system usually provides only limited insight into the dynamics and function of the system as a whole. A complete understanding requires not only knowledge of the transient and steady-state structures at near-atomic details; it also requires knowledge of structural pathways and ligand interactions in a cellular context.
Due to dramatic improvements in experimental ...