Cell signaling encompasses a host of processes that transmit chemical signals, such as hormonal stimuli, from the outside world into biological cells, eventually causing responses on the level of gene expression. Cascades of protein-protein interactions transmit these signals which often originate at the plasma membrane that forms the envelope of the cell.

Such processes are currently the object of intense studies in biomedical research because, when they fail, they can cause disease. Understanding these processes at the molecular level can also reveal a better understanding of how cells are organized.

One particular signaling pathway involves the oncoprotein KRas. Deficiencies in this process notoriously lead to a family of tumors that remain untreatable because it is still unknown how Ras proteins activate the effectors that form its downstream targets.

The Lösche group at CMU Physics designed artificial membrane systems that are realistic physical models of biological membranes and optimized these systems for investigations with specular neutron reflectometry. NR is a mode of neutron scattering in which a highly collimated neutron beam is reflected from an atomically smooth carrier substrate that supports a single bilayer membrane. The group has also optimized data evaluation procedures and developed techniques to interpret NR results in the context of high-resolution protein structures from x-ray crystallography or NMR spectroscopy.

CMU Physics Associate Research Professor Frank Heinrich and coworkers in the CMU Physics Department now determined a draft structure of KRas with its downstream effector RAF-RBD. Together with Dr. A. Stephen and collaborators within the Ras Initiative located at the National Cancer Institute, they plan to investigate the details of KRas interactions with its related adaptor and effector proteins on the membrane in the scope of this project.