鉴定和功能表征ANKRD11 中的二分核定位信号。
Identification and functional characterization of a bipartite nuclear localization signal in ANKRD11.
机构信息
Biomedical Research Institute, Shenzhen-Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.
Greater Bay Biomedical InnoCenter, Shenzhen Bay Laboratory, Shenzhen, 518107, China.
出版信息
Biochem Biophys Res Commun. 2023 Aug 30;670:117-123. doi: 10.1016/j.bbrc.2023.05.046. Epub 2023 May 15.
ANKRD11 gene encodes for the large nuclear protein essential for multiple system development including the nervous system. However, the molecular basis for the proper nuclear localization of ANKRD11 has not yet been elucidated. In this study, we have identified a functional bipartite nuclear localization signal (bNLS) between residues 53 and 87 of ANKRD11. Using biochemical approaches, we discovered two major binding sites in this bipartite NLS for Importin α1. Through site-directed mutagenesis and functional analysis, we further found that this bipartite NLS is sufficient for nuclear import of overexpressing GFP in HeLa cells and necessary for nuclear localization of ANKRD11. Importantly, our study provides a possible pathogenic mechanism for certain clinical variants located within the bipartite nuclear localization signal of ANKRD11.
ANKRD11 基因编码的大型核蛋白对于包括神经系统在内的多个系统的发育至关重要。然而，ANKRD11 正确核定位的分子基础尚未阐明。在这项研究中，我们确定了 ANKRD11 第 53 至 87 位氨基酸之间具有功能性的双组分核定位信号（bNLS）。通过生化方法，我们在该双组分 NLS 中发现了 Importin α1 的两个主要结合位点。通过定点突变和功能分析，我们进一步发现该双组分 NLS 足以实现 GFP 在 HeLa 细胞中的核输入，并且对于 ANKRD11 的核定位是必需的。重要的是，我们的研究为位于 ANKRD11 双组分核定位信号内的某些临床变异体提供了一种可能的致病机制。
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