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Structural Characterization of NRAS Isoform 5

Overview
Journal Protein Sci
Specialty Biochemistry
Date 2016 Mar 8
PMID 26947772
Citations 5
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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.

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References
1.
Krissinel E, Henrick K . Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2256-68. DOI: 10.1107/S0907444904026460. View

2.
Sondak V, Gibney G . Indications and options for systemic therapy in melanoma. Surg Clin North Am. 2014; 94(5):1049-58, viii. DOI: 10.1016/j.suc.2014.07.007. View

3.
Fersht A . Helix stability in barstar peptides. Eur J Biochem. 1997; 249(3):724-32. DOI: 10.1111/j.1432-1033.1997.t01-1-00724.x. View

4.
Cantwell-Dorris E, OLeary J, Sheils O . BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 2011; 10(3):385-94. DOI: 10.1158/1535-7163.MCT-10-0799. View

5.
Lee W, Westler W, Bahrami A, Eghbalnia H, Markley J . PINE-SPARKY: graphical interface for evaluating automated probabilistic peak assignments in protein NMR spectroscopy. Bioinformatics. 2009; 25(16):2085-7. PMC: 2723000. DOI: 10.1093/bioinformatics/btp345. View