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

Poster Board Number: A164

Nathan Nowling (Metropolitan State University of Denver), Elizabeth Spear (Metropolitan State University of Denver), Natasia Paukovich (University of Colorado, Anschutz Medical Campus), John Manalastas (Metropolitan State University of Denver), Beat Vögeli (University of Colorado, Anschutz Medical Campus), Megan Filbin (Metropolitan State University of Denver)

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.

Support or Funding Information

Research reported in this poster was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number R15GM134393 to M. E. Filbin; Metropolitan State University of Denver Undergraduate Research amp; Creative Scholarship Program Mini-grant to N. Nowling.

Research reported in this poster was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number R15GM134393 to M. E. Filbin; Metropolitan State University of Denver Undergraduate Research amp;amp; Creative Scholarship Program Mini-grant to N. Nowling.