Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.
Department of Biochemistry, School of Medicine, University of Patras, GR-26504 Patras, Greece.
Int J Mol Sci. 2023 Jan 29;24(3):2572. doi: 10.3390/ijms24032572.
The La protein (lupus antigen) is a ubiquitous RNA-binding protein found in all human cells. It is mainly localized in the nucleus, associates with all RNA polymerase III (Pol III) transcripts, as the first factor they interact with, and modulates subsequent processing events. Export of La to the cytoplasm has been reported to stimulate the decoding of specific cellular and viral mRNAs through IRES-dependent (Internal ribosome entry site) binding and translation. Using NMR (Nuclear Magnetic Resonance) spectroscopy, we provide atomic-level-resolution structural insights on the dynamical properties of human La (hLa) protein in solution. Moreover, using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we provide evidence about the role and ligand specificity of the C-terminal domain of the La protein (RRM2 and C-terminal region) that could mediate the recognition of HCV-IRES.
La 蛋白（狼疮抗原）是一种普遍存在的 RNA 结合蛋白，存在于所有人类细胞中。它主要定位于细胞核内，与所有 RNA 聚合酶 III（Pol III）转录本结合，作为它们首先相互作用的因子，并调节随后的加工事件。据报道，La 蛋白向细胞质的输出通过 IRES 依赖性（内部核糖体进入位点）结合和翻译来刺激特定细胞和病毒 mRNA 的解码。使用 NMR（核磁共振）光谱，我们提供了关于人 La（hLa）蛋白在溶液中动态特性的原子分辨率结构见解。此外，使用 NMR 光谱和等温滴定量热法（ITC）的组合，我们提供了有关 La 蛋白 C 末端结构域（RRM2 和 C 末端区域）的作用和配体特异性的证据，该结构域可能介导 HCV-IRES 的识别。
