Structural characterization of NRAS isoform 5.
Markowitz J, Mal TK, Yuan C, Courtney NB, Patel M, Stiff AR, Blachly J, Walker C, Eisfeld AK, de la Chapelle A, Carson WE 3rd
Protein Sci 25 1069-74 05/01/2016
It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix-turn-coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.Full Text