RAS internal tandem duplication disrupts GTPase-activating protein (GAP) binding to activate oncogenic signaling [Genomics and Proteomics]

We present the first crystal structures of NRAS and KRAS ITD at 1.65–1.75 Å resolution, respectively, providing insight into the physical interactions of this class of RAS variants with its regulatory and effector proteins. Our in-depth bedside-to-bench analysis uncovers the molecular mechanism underlying a case of highly aggressive colorectal cancer and illustrates the importance of robust biochemical and biophysical approaches in the implementation of individualized medicine.

Source: Journal of Biological Chemistry - July 9, 2020 Category: Chemistry Authors: Andrew C. Nelson, Thomas J. Turbyville, Srisathiyanarayanan Dharmaiah, Megan Rigby, Rendong Yang, Ting-You Wang, John Columbus, Robert Stephens, Troy Taylor, Drew Sciacca, Getiria Onsongo, Anne Sarver, Subbaya Subramanian, Dwight V. Nissley, Dhirendra K. Tags: Protein Structure and Folding Source Type: research