Build your own yeast cell

German researchers piece together biological jigsaw.

In an attempt to bridge the gap between the detailed structures of specific molecules created by structural biology and the low resolution images of large complexes provided by cell biology, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have started to piece together the jigsaw of the cell. They have reconstructed large-scale assemblies from those detailed structures and interactions that are known or at least predictable. The resulting hypothetical assemblies can readily be tested by conventional methods of molecular biology.

Robert Russell and his collaborators at the EMBL and at the German company Cellzome analysed the protein-protein interactions in baker’s yeast, which is one of the best-studied organisms in this respect. Using existing data from a variety of interaction measures, they aimed to define ’complexes’ as generously as possible, in marked contrast to the approach of crystallographers, who tend to trim off the loose and uncertain bits before submitting the remaining ’core complex’ to structural analysis. Then they tried to reconstruct in as much detail as possible the molecular structures of these complexes, using known structures of individual proteins or domains and predictions based on homology with other proteins. In the final step, they matched the shapes of the resulting complexes to the shapes of cellular structures observed in electron microscopy.

The complexes that could thus be put together and studied include the RNA polymerase II (of which a slimmed-down version is characterised by crystallography); a chaperonin with associated factors; the RNase P complex; and the Ski complex, which is involved in degrading messenger RNA. While the large-scale structures resulting from this work have to be regarded as hypothetical for the time being, they can be readily tested by classic methods including site-directed mutagenesis. It is a bold step towards understanding the molecular machinery of the entire cell.

Michael Gross