Sessler Richard J, Noy Noa
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
Mol Cell. 2005 Apr 29;18(3):343-53. doi: 10.1016/j.molcel.2005.03.026.
Primary sequences of proteins often contain motifs that serve as "signatures" for subcellular targeting, such as a nuclear localization signal (NLS). However, many nuclear proteins do not harbor a recognizable NLS, and the pathways that mediate their nuclear translocation are unknown. This work focuses on CRABP-II, a cytosolic protein that moves to the nucleus upon binding of retinoic acid. While CRABP-II does not contain an NLS in its primary sequence, such a motif could be recognized in the protein's tertiary structure. We map the retinoic acid-induced structural rearrangements that result in the presence of this NLS in holo- but not apo-CRABP-II. The signal, whose three-dimensional configuration aligns strikingly well with a "classical" NLS, mediates ligand-induced association of CRABP-II with importin alpha and is critical for nuclear localization of the protein. The ligand-controlled NLS "switch" of CRABP-II may represent a general mechanism for posttranslational regulation of the subcellular distribution of a protein.
蛋白质的一级序列通常包含作为亚细胞靶向“标记”的基序，例如核定位信号（NLS）。然而，许多核蛋白并不具有可识别的NLS，介导其核转运的途径尚不清楚。这项工作聚焦于CRABP-II，一种在视黄酸结合后转移至细胞核的胞质蛋白。虽然CRABP-II在其一级序列中不包含NLS，但在该蛋白的三级结构中可能识别出这样的基序。我们绘制了视黄酸诱导的结构重排，这种重排在全反式视黄酸结合蛋白-II（holo-CRABP-II）而非脱辅基视黄酸结合蛋白-II（apo-CRABP-II）中导致了这种NLS的存在。该信号的三维构型与“经典”NLS惊人地吻合，介导了视黄酸诱导的CRABP-II与输入蛋白α的结合，并且对于该蛋白的核定位至关重要。CRABP-II的配体控制的NLS“开关”可能代表了一种蛋白质亚细胞分布的翻译后调控的普遍机制。
