Transportin-1(Trn1),也称为核蛋白β2(Kapβ2),可能是在Importin-β之后,核动力蛋白-β家族的特征最好的核输入受体,但是它在细胞中的某些功能仍然令人困惑或刚刚出现。自25年前首次确认Trn1为hnRNPA1的核输入受体以来,一些分子和结构研究揭示并完善了我们对Trn1介导的核导入的理解.特别是,在分子水平上对Trn1对NLS识别的理解,随着一类新的NLS被称为PY-NLS的识别,迈出了决定性的一步。它们构成了Trn1的最佳特征底物。除了PY-NLS,许多Trn1货物港口的NLS与原型PY-NLS不同,这使得Trn1对货物识别的全球理解变得复杂。虽然PY-NLS识别已经很好地建立并得到了几个结构的支持,Trn1对非PY-NLS的识别知之甚少,但最近的报道已经开始揭示对这种NLS的认识。除了其作为核进口受体的主要和长期的活性,Trn1最近被证明是在核进口之外的月光下。例如,Trn1参与了病毒脱衣,纤毛运输和调节易聚集蛋白的相分离特性。这里,我们专注于Trn1介导的核进口的结构和功能方面,以及Trn1的月光活动。
Transportin-1 (Trn1), also known as karyopherin-β2 (Kapβ2), is probably the best-characterized nuclear import receptor of the karyopherin-β family after Importin-β, but certain aspects of its functions in cells are still puzzling or are just recently emerging. Since the initial identification of Trn1 as the nuclear import receptor of hnRNP A1 ∼25 years ago, several molecular and structural studies have unveiled and refined our understanding of Trn1-mediated nuclear import. In particular, the understanding at a molecular level of the NLS recognition by Trn1 made a decisive step forward with the identification of a new class of NLSs called PY-NLSs, which constitute the best-characterized substrates of Trn1. Besides PY-NLSs, many Trn1 cargoes harbour NLSs that do not resemble the archetypical PY-NLS, which complicates the global understanding of cargo recognition by Trn1. Although PY-NLS recognition is well established and supported by several structures, the recognition of non-PY-NLSs by Trn1 is far less understood, but recent reports have started to shed light on the recognition of this type of NLSs. Aside from its principal and long-established activity as a nuclear import receptor, Trn1 was shown more recently to moonlight outside nuclear import. Trn1 has for instance been caught in participating in virus uncoating, ciliary transport and in modulating the phase separation properties of aggregation-prone proteins. Here, we focus on the structural and functional aspects of Trn1-mediated nuclear import, as well as on the moonlighting activities of Trn1.