Structural Investigation of a Putative Intrinsically Disordered Region Within Deleted in Colorectal Carcinoma That Regulates Protein Synthesis

Abstract

Intrinsically disordered proteins (IDPs) are key players in cell signaling, gene expression networks, and cellular development – to include spatiotemporally‐controlled protein synthesis. The intracellular, C‐terminal tail of the chemotropic receptor, Deleted in Colorectal Carcinoma (DCC), is a predicted IDP that stalls translation machinery at axon growth‐cone membranes. DCC releases the translation machinery (via an unknown mechanism) when it encounters its specific ligand Netrin‐1, initiating local protein synthesis and axonal outgrowth. Using mutational analysis coupled with in vitro translation reporter assays, we have identified a portion of DCC’s C‐terminal tail that is important for translation stalling. To determine any structure and dynamics of this putative IDP, we are recombinantly expressing and purifying the protein for analysis via NMR. Our analysis will shed light on how protein structural plasticity and dynamics play a role in regulating important cellular processes and may provide avenues for predictive modeling and target identification of IDPs that regulate translation.