At present, there is a gap in our structural understanding of cellular complexes. We have comparatively low-resolution images of large cellular complexes — for example, electron microscopy (EM) images of the nuclear pore complex — and high-resolution structures of components of these complexes. As it seems that technical limitations will prevent us from obtaining high-resolution structures of large complexes in the immediate future, how can we begin to bridge this gap? Russell and colleagues now describe one way in Science.
They modelled a large set of yeast protein-interaction data using known three-dimensional structures, and were able to obtain the most complete view of protein complexes so far and also to predict a structure-based network of crosstalk between complexes. Furthermore, they screened complexes using EM to obtain low-resolution images that helped them to assemble and confirm their models. Of 102 complexes, at least 54 partial models could be obtained. And, for 29 of these — including the exosome, RNA polymerase II and a 3′-messenger-RNA-degradation complex — the results revealed atomic details that would not readily have been seen by homology. These models have the potential to generate hypotheses that can be further tested, for example, by mutagenesis. In addition, as each new structure that becomes available can help us to understand numerous interactions, “The complex predictions and the associated network will ... improve exponentially as the numbers of structures and interactions increase, providing an ever more complete molecular anatomy of the cell.” REFERENCE Aloy, P. et al. Structure-based assembly of protein complexes in yeast. Science 303, 2026–2029 (2004)
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