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NRAS同工型5的结构表征

Structural characterization of NRAS isoform 5.

作者信息

Markowitz Joseph, Mal Tapas K, Yuan Chunhua, Courtney Nicholas B, Patel Mitra, Stiff Andrew R, Blachly James, Walker Christopher, Eisfeld Ann-Kathrin, de la Chapelle Albert, Carson William E

机构信息

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.

出版信息

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.

摘要

最近发现NRAS亚型5(20个氨基酸)在黑色素瘤中表达,并导致更具侵袭性的细胞表型。这种新型亚型导致下游靶点如AKT、MEK和ERK的磷酸化增加以及细胞增殖增加。本结构报告描述了NRAS亚型5的核磁共振溶液结构,作为理解其生物物理相互作用的起点。该亚型在水溶液中高度灵活,但通过核磁共振和圆二色光谱法测定,在三氟乙醇存在下形成螺旋-转角-螺旋结构。

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