Structural characterization of NRAS isoform 5

Protein Sci. 2016 May;25(5):1069-74. doi: 10.1002/pro.2916. Epub 2016 Mar 24.

Abstract

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.

Keywords: NMR; NRAS; isoform; melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Melanoma / genetics
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphorylation
  • Protein Conformation, alpha-Helical
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Skin Neoplasms / genetics
  • Trifluoroethanol / chemistry*

Substances

  • Membrane Proteins
  • Protein Isoforms
  • Trifluoroethanol
  • GTP Phosphohydrolases
  • NRAS protein, human