The topology of protein-protein interactions in situ in eukaryotic cells

Division Of Basic Sciences - Nci

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Abstract

We have now proven the concept of crosslinking complexes in cells and discovered novel subunits of complexes that were thought to be well-characterized. Our test case has been the proteasome. The next stage is to scale up this developed approach to get maps of entire organelles and to discover new protein complexes related to disease. We are also targeting the interaction network of the proto-oncoprotein MYC. MYC's disorder and 'stickiness' have both served to frustrate confident identification of binders and mapping their binding site. Crosslinking MS will discover these PPIs with residue-level structural information and so suggest potential avenues for their therapeutic disruption.