Determine the structure of the KRAS:BRAF complex on tethered lipid bilayers using neutron reflectivity

Ras genes are the most frequently mutated oncogenes in human cancer, and the KRAS isoform is mutated in 95% of pancreatic cancer. KRAS is peripherally localized at the plasma membrane and, when activated, binds effector proteins such as BRAF. KRAS signaling is enhanced during cancer, and the KRAS/BRAF complex at the lipid membrane is a high-value target in the search for intervening drugs. This proposal seeks to obtain a low-resolution structure of the KRAS/BRAF complex using neutron reflectometry as part of a broader biophysical characterization effort of this potential drug target. Neutron reflectometry is one of the few techniques that yield structural information on this class of peripheral and conformational flexible membrane proteins and is essential for this effort.