Prof. Jürgen M. Plitzko

Dept Struct Biol, Max Planck Institute of Biochemistry, Martinsried, Germany


3 dimensional cryo-electron microscopy (3DEM):

Voyages to uncharted molecular territories




Cryo-electron tomography (cryo-ET) of whole cells allows us to investigate the structure-function
relationship of molecular complexes and supramolecular assemblies in their native environment. It
thus makes a fundamental change in the way we approach biochemical processes that underlie and
orchestrate higher cellular functions. In the past, molecular interactions were studied mostly in a
collective manner, whereas now we have the tools to visualize the interactions between individual
molecules in their unperturbed functional environments. Although they share common underlying
principles, no two cells or organelles are identical, owing to the inherent stochasticity of
biochemical processes in cells as well as their functional diversity. Therefore, it will be a major
challenge to extract generic features from the three dimensional maps, such as the modes of
interaction between molecular species. However, the ultimate goal, the discovery of general rules
that underlie cellular processes, has to go beyond observing qualitative features and has to be
based on stringent analytical criteria combining the information gathered from different methods
for a complete integrative analysis.

Merging the power of identification (e.g. by quantitative mass spectrometry or correlative light
microscopy) with advanced preparation techniques (e.g. focused ion beam milling) while utilizing
the power of visualization techniques (by cryo-ET/EM approaches) is definitely a 'nouvelle route'
with a great potential in the field of molecular structural biology that promises to provide a
non-invasive and deep insight into the functional organization of cellular proteomes).