North Carolina State University scientists examining the atomic resolution structures of a protein that has a mutated form associated with cancer have discovered why protein-protein interactions with the mutant form lead to uncontrolled cell proliferation.

A mutation in the 61st amino acid of the Ras protein is commonly observed in cancer cells, but researchers had not been able to identify why the mutated protein behaved differently in cells than the non-mutated protein. They also did not know why mutated Ras behaved differently in isolation than it did within cells.

By looking at how the normal and mutant proteins folded, by themselves or in the presence of other proteins, the NCSU scientists could see how a combination of the 61st amino acid mutation along with the presence of another protein, Raf, could together keep a cellular switch from turning off.

Dr. Carla Mattos explained their findings: “We all knew that there had to be something in the cell not accounted for by the studies in isolated Ras. We now know that at least part of that something is the Raf protein. When the defective Ras encounters Raf, the switch becomes inaccessible and the highly controlled cell proliferation system is broken, leading to uncontrolled cell proliferation and cancer.”