Resonance assignment and secondary structure of an N-terminal fragment of the human La protein
Resonance assignment and secondary structure of an N-terminal fragment of the human La protein
复制标题
DOI：
10.1023/a:1024741228802
复制
发表时间：
2003-09-01
影响因子：
2.7
通讯作者：
Conte, MR
中科院分区：
文献类型：
--
作者：
Alfano, C;Babon, J;Conte, MR
La蛋白是一种丰富的RNA结合磷蛋白，最初被描述为系统性红斑狼疮和干燥综合征患者的自身抗原。 La 在真核细胞中普遍存在，主要定位于细胞核，与新生 RNA 聚合酶 III 转录本的 UUU-OH 3 末端结合，稳定它们，防止外切核酸消化并确保正确的成熟过程（Maraia 和 Intine，2001；Wolin 和 Cedervall，2002）。高亲和力 Poly (U) 识别位于人 La (hLa) 的 N 端结构域 (NTD)，从脊椎动物到酵母高度保守，而 hLa C 端结构域已被证明在 RNA 核保留和 5-ppp-RNA 识别中发挥关键作用。有趣的是，La 还与大量病毒和细胞 mRNA 相关，这些 mRNA 实际上并不以 3 聚 (U) 结尾或包含 3 聚 (U)，并且似乎在 mRNA 翻译的调节中被招募（至少在某些情况下），但其功能和作用模式仍然难以捉摸（Maraia 和 Intine，2001；Wolin 和 Cedervall，2002）。 La 蛋白的 NTD 预计包含两个 RNA 识别基序 (RRM)，这两个基序对于聚 (U) 结合都至关重要；然而，一些作者质疑第一个结构域，称为“La-motif”，折叠成主要是螺旋结构（Wolin 和 Cedervall，2002）。在这里，我们报告了 hLa 的 RRM2 的基本完整分配并描绘了其二级结构。对结构的洞察
The La protein is an abundant RNA-binding phosphoprotein originally described as an autoantigen in systemic lupus erythematosus and Sjogren’s syndrome patients. Ubiquitous in eukaryotic cells, La localises predominantly in the nucleus where it associates with the UUU-OH 3 terminus of nascent RNA polymerase III transcripts, stabilising them against exonucleolytic digestion and ensuring the correct maturation process (Maraia and Intine, 2001; Wolin and Cedervall, 2002). High affinity poly (U) recognition resides in the N-terminal domain (NTD) of human La (hLa), highly conserved from vertebrates to yeasts, whereas hLa C-terminal domain has been shown to play a key role in RNA nuclear retention and 5-ppp-RNA recognition. Interestingly, La also associates with a large number of viral and cellular mRNAs which do not in fact end in or contain a 3 poly (U), and appears to be recruited (at least in some cases) in regulation of mRNA translation, but its function and mode of action remain elusive (Maraia and Intine, 2001; Wolin and Cedervall, 2002). The NTDs of La proteins are predicted to contain two RNA recognition motifs (RRM) that are both critical for poly (U) binding; however, some authors contest that the first domain, called the ‘La-motif’, folds into a predominantly helical structure (Wolin and Cedervall, 2002). Here we report the essentially complete assignment for the RRM2 of hLa and delineate its secondary structure. Insights into the structure of the