Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals

• Published in: eLife 2019-04, Vol.8
• Main Authors: Li, Yuling, Zhou, Jinhan, Min, Sui, Zhang, Yang, Zhang, Yuqing, Zhou, Qiao, Shen, Xiaofei, Jia, Da, Han, Junhong, Sun, Qingxiang
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; animal; Animals; Biochemistry and Chemical Biology; Cancer; Collaboration; Cytoplasm; distinct mechanism; Exportin 1 Protein; Exports; Fungi; Humans; Karyopherins - metabolism; Laboratories; Mice; nuclear export signal; Nuclear Proteins - metabolism; Nuclear transport; Protein Binding; Protein Multimerization; Proteins; ran GTP-Binding Protein - metabolism; RanBP1; Receptors, Cytoplasmic and Nuclear - metabolism; Saccharomyces cerevisiae; Structural Biology and Molecular Biophysics; Yeast
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.41331

Ran binding protein 1 (RanBP1) is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport. Much of what we know about RanBP1 is learned from fungi. Intrigued by the long-standing paradox of harboring an extra NES in animal RanBP1, we discovered utterly unexpected cargo dissociation and nuclear export mechanisms for animal RanBP1. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequestered RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP formed a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP formed a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals was the loss of affinity between RanBP1-RanGTP and CRM1, since residues mediating their interaction in fungi were not conserved in animals. The biological significances of these different mechanisms in fungi and animals were also studied.