Department of Biology (D-BIOL), Institute of Biochemistry (IBC), ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland and MLS Program, Life Sciences Zurich Graduate School, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Nucleic Acids Res. 2013 Sep;41(17):8266-79. doi: 10.1093/nar/gkt675. Epub 2013 Jul 31.
Multiple export receptors passage bound pre-ribosomes through nuclear pore complexes (NPCs) by transiently interacting with the Phe-Gly (FG) meshwork of their transport channels. Here, we reveal how the non-FG interacting yeast mRNA export factor Gly-Leu-FG lethal 2 (Gle2) functions in the export of the large pre-ribosomal subunit (pre-60S). Structure-guided studies uncovered conserved platforms used by Gle2 to export pre-60S: an uncharacterized basic patch required to bind pre-60S, and a second surface that makes non-FG contacts with the nucleoporin Nup116. A basic patch mutant of Gle2 is able to function in mRNA export, but not pre-60S export. Thus, Gle2 provides a distinct interaction platform to transport pre-60S to the cytoplasm. Notably, Gle2's interaction platforms become crucial for pre-60S export when FG-interacting receptors are either not recruited to pre-60S or are impaired. We propose that large complex cargos rely on non-FG as well as FG-interactions for their efficient translocation through the nuclear pore complex channel.
多个出口受体通过与运输通道的苯丙氨酸-甘氨酸 (FG) 网格结构短暂相互作用，将预核糖体复合物穿过核孔复合物 (NPC)。在这里，我们揭示了非 FG 相互作用的酵母 mRNA 出口因子 Gly-Leu-FG 致死 2 (Gle2) 如何在大预核糖体亚基 (pre-60S) 的出口中发挥作用。结构导向研究揭示了 Gle2 用于出口 pre-60S 的保守平台：一个未被表征的碱性斑块，用于结合 pre-60S，以及第二个表面，与核孔蛋白 Nup116 形成非 FG 接触。Gle2 的碱性斑块突变体能够在 mRNA 出口中发挥作用，但不能在 pre-60S 出口中发挥作用。因此，Gle2 提供了一个独特的相互作用平台，将 pre-60S 运输到细胞质。值得注意的是，当 FG 相互作用受体既未被招募到 pre-60S 上也未受损时，Gle2 的相互作用平台对 pre-60S 出口变得至关重要。我们提出，大型复杂货物依赖于非 FG 以及 FG 相互作用，以使其有效地通过核孔复合物通道转运。
