6q84
From Proteopedia
Crystal structure of RanGTP-Pdr6-eIF5A export complex
Structural highlights
Function[KA122_YEAST] Nuclear transport factor (karyopherin) involved in protein transport between the cytoplasm and nucleoplasm. Required for the nuclear import of the complex composed the large subunit (TOA1) and the small subunit (TOA2) of the general transcription factor IIA (TFIIA). Required for the nuclear import of the RNR2-RNR4 heterodimer, also called beta-beta' subunit, which corresponds to the small subunit of the ribonucleotide reductase (RNR). May play a role in regulation of pleiotropic drug resistance.[1] [2] [3] [4] [IF5A1_YEAST] mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. Essential for polarized growth, a process necessary for G1/S transition. May mediate large range of effects of the polyamine spermidine in the cell.[5] [6] [7] [8] [9] [10] [11] [12] [13] [RAN_HUMAN] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.[14] [15] [16] [17] Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.[18] [19] [20] [21] Publication Abstract from PubMedImportins ferry proteins into nuclei while exportins carry cargoes to the cytoplasm. In the accompanying paper in this issue (Vera Rodriguez et al. 2019. J. Cell Biol. https://doi.org/10.1083/jcb.201812091), we discovered that Pdr6 is a biportin that imports, e.g., the SUMO E2 ligase Ubc9 while depleting the translation factor eIF5A from the nuclear compartment. In this paper, we report the structures of key transport intermediates, namely, of the Ubc9*Pdr6 import complex, of the RanGTP*Pdr6 heterodimer, and of the trimeric RanGTP*Pdr6*eIF5A export complex. These revealed nonlinear transport signals, chaperone-like interactions, and how the RanGTPase system drives Pdr6 to transport Ubc9 and eIF5A in opposite directions. The structures also provide unexpected insights into the evolution of transport selectivity. Specifically, they show that recognition of Ubc9 by Pdr6 differs fundamentally from that of the human Ubc9-importer Importin 13. Likewise, Pdr6 recognizes eIF5A in a nonhomologous manner compared with the mammalian eIF5A-exporter Exportin 4. This suggests that the import of Ubc9 and active nuclear exclusion of eIF5A evolved in different eukaryotic lineages more than once and independently from each other. Structural basis for the nuclear import and export functions of the biportin Pdr6/Kap122.,Aksu M, Trakhanov S, Vera Rodriguez A, Gorlich D J Cell Biol. 2019 Apr 25. pii: jcb.201812093. doi: 10.1083/jcb.201812093. PMID:31023722[22] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations 5 reviews cite this structure No citations found References
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