Yamagishi Ryosuke, Okuyama Takahide, Oba Shuntaro, Shimada Jiro, Chaen Shigeru, Kaneko Hiroki
Department of Integrated Sciences in Physics and Biology, College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajousui, Setagaya, Tokyo 156-8550, Japan.
Graduate School of Integrated Basic Sciences, Nihon University, 3-25-40 Sakurajousui, Setagaya-ku, Tokyo 156-8550, Japan.
Biochem Biophys Rep. 2015 Nov 9;4:392-396. doi: 10.1016/j.bbrep.2015.11.001. eCollection 2015 Dec.
Most transcription and epigenetic factors in eukaryotic cells have nuclear localization signals (NLSs) and are transported to the nucleus by nuclear transport proteins. Understanding the features of NLSs and the mechanisms of nuclear transport might help understand gene expression regulation, somatic cell reprogramming, thus leading to the treatment of diseases associated with abnormal gene expression. Although many studies analyzed the amino acid sequence of NLSs, few studies investigated their three-dimensional structure. Therefore, we conducted a statistical investigation of the dynamic structure of NLSs by extracting the conformation of these sequences from proteins examined by X-ray crystallography and using a quantity defined as conformational determination rate (a ratio between the number of amino acids determining the conformation and the number of all amino acids included in a certain region). We found that determining the conformation of NLSs is more difficult than determining the conformation of other regions and that NLSs may tend to form more heteropolymers than monomers. Therefore, these findings strongly suggest that NLSs are intrinsically disordered regions.
真核细胞中的大多数转录因子和表观遗传因子都具有核定位信号（NLSs），并通过核转运蛋白被转运到细胞核中。了解NLSs的特征和核转运机制可能有助于理解基因表达调控、体细胞重编程，从而治疗与基因表达异常相关的疾病。尽管许多研究分析了NLSs的氨基酸序列，但很少有研究探究其三维结构。因此，我们通过从X射线晶体学检测的蛋白质中提取这些序列的构象，并使用一个定义为构象确定率（确定构象的氨基酸数量与特定区域中所有氨基酸数量的比率）的量，对NLSs的动态结构进行了统计研究。我们发现，确定NLSs的构象比确定其他区域的构象更困难，并且NLSs可能比单体更容易形成更多的异聚物。因此，这些发现有力地表明NLSs是内在无序区域。
