The orientation of RIT1 on tethered bilayer lipid membranes using neutron reflectivity.

Rit1 is a signaling protein whose orientation at the membrane is vital for a mechanistic understanding of human cancer. Neutron reflectometry (NR) is among the few techniques that can structurally characterize this protein under physiologically relevant biomimetic conditions at the lipid membrane. We will conduct a series of NR measurements with increasing concentrations of Rit1 using a model membrane, which will characterize the conformation of the protein at the membrane as a function of crowding. This work is a direct continuation of our recent research on the functionally related KRAS protein (Van, Q. N. et al. Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane. Proc National Acad Sci 117, 24258–24268 (2020)).