title: Structural characterization of NRAS isoform 5.
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.
authors.affiliation: Moffitt Cancer Center Department of Cutaneous Oncology, The Ohio State University, Columbus, Ohio.|The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Joseph
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: The Ohio State University Campus Chemical Instrument Center-NMR, The Ohio State University, Columbus, Ohio.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Mal
authors.affiliation: The Ohio State University Campus Chemical Instrument Center-NMR, The Ohio State University, Columbus, Ohio.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yuan
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Courtney
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Mitra
authors.initials: M
authors.lastname: Patel
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Stiff
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: James
authors.initials: J
authors.lastname: Blachly
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Walker
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Eisfeld
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.affiliation: The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.|The Ohio State University Wexner Medical Center Department of Surgery, The Ohio State University, Columbus, Ohio.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D002942:Circular Dichroism; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D000072756:Protein Conformation, alpha-Helical; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics; D014270:Trifluoroethanol / Q000737:chemistry*
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; D014270:Trifluoroethanol; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: NMR; NRAS; isoform; melanoma