Genome-scale identification of protein docking interactions

Type of Award: catalyst
Award Number:
Award Period: August 2012 - July 2013
Amount Awarded: $ 197,394.00
PI(s): Brian Kay, PhD, UIC; Eric Weiss, PhD, NU; Milan Mrksich, PhD, NU;

Abstract: Networks of interacting proteins inside cells direct their behavior. When functioning properly, these systems ensure correct organization and function of cells in normal tissues. In contrast, their derangement can lead to deadly and debilitating illnesses, notably cancer and age-related disorders. It is therefore critical to understand the rules that govern protein interactions in both healthy and diseased cells. A specific class of interactions has proven both centrally important and incredibly difficult to identify and study: brief, dynamic associations through short "docking motifs". In essence, these motifs are like "words" through which proteins recognize each other. Such interactions are critical for proper function, as they localize proteins such as kinases to different parts of the cell and contribute to substrate specificity. Using a new computational method, we found that there are probably hundreds more of these words than previously understood. For the vast majority of them no function is known. This project will develop and combine two new approaches to study thousands of these potential docking motif interactions in a single experiment. The groups of Milan Mrksich at NWU and Brian Kay at UIC will pursue these novel screening approaches, and the group of Eric Weiss at NWU will develop ways to parallelize production of proteins for analysis. Overall, this promises to provide unique insight into a crucial part of cellular "wiring diagrams" that is currently missing from contemporary molecular biology.