Department of Molecular Biology, Faculty of Medicine, GZMB, Georg-August-University Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany.
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, GZMB, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, D-37077 Göttingen, Germany.
Biol Chem. 2023 May 22;404(8-9):791-805. doi: 10.1515/hsz-2023-0155. Print 2023 Jul 26.
Soluble nuclear transport receptors and stationary nucleoporins are at the heart of the nucleocytoplasmic transport machinery. A subset of nucleoporins contains characteristic and repetitive FG (phenylalanine-glycine) motifs, which are the basis for the permeability barrier of the nuclear pore complex (NPC) that controls transport of macromolecules between the nucleus and the cytoplasm. FG-motifs can interact with each other and/or with transport receptors, mediating their translocation across the NPC. The molecular details of homotypic and heterotypic FG-interactions have been analyzed at the structural level. In this review, we focus on the interactions of nucleoporins with nuclear transport receptors. Besides the conventional FG-motifs as interaction spots, a thorough structural analysis led us to identify additional similar motifs at the binding interface between nucleoporins and transport receptors. A detailed analysis of all known human nucleoporins revealed a large number of such phenylalanine-containing motifs that are not buried in the predicted 3D-structure of the respective protein but constitute part of the solvent-accessible surface area. Only nucleoporins that are rich in conventional FG-repeats are also enriched for these motifs. This additional layer of potential low-affinity binding sites on nucleoporins for transport receptors may have a strong impact on the interaction of transport complexes with the nuclear pore and, thus, the efficiency of nucleocytoplasmic transport.
可溶性核转运受体和固定核孔蛋白是核质转运机制的核心。一组核孔蛋白包含特征性和重复的 FG（苯丙氨酸-甘氨酸）基序，这是核孔复合物（NPC）渗透屏障的基础，控制着核质之间大分子的运输。FG 基序可以相互作用，也可以与转运受体相互作用，介导它们穿过 NPC 的易位。同质和异质 FG 相互作用的分子细节已在结构水平上进行了分析。在这篇综述中，我们专注于核孔蛋白与核转运受体的相互作用。除了作为相互作用点的传统 FG 基序外，彻底的结构分析使我们能够在核孔蛋白和转运受体的结合界面上识别其他类似的基序。对所有已知人类核孔蛋白的详细分析揭示了大量这样的含有苯丙氨酸的基序，它们没有埋藏在各自蛋白质的预测 3D 结构中，而是构成了溶剂可及表面积的一部分。只有富含传统 FG 重复序列的核孔蛋白才富含这些基序。核孔蛋白上这些转运受体的潜在低亲和力结合位点的额外层可能对转运复合物与核孔的相互作用，从而对核质转运的效率产生重大影响。
