Structural Insights into How Yrb2p Accelerates the Assembly of the Xpo1p Nuclear Export Complex

Koyama, Michihisa; Shirai, Natsuki; Matsuura, Yasushi

doi:10.1016/j.celrep.2014.09.052

Cited by 37 publications

(39 citation statements)

References 46 publications

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“…2D) was very similar to the previously determined structure of the Xpo1p-PKI-Gsp1p-GTP complex (PDB code, 3WYG; Koyama et al 2014) with Ca r.m.s.d. 2D) was very similar to the previously determined structure of the Xpo1p-PKI-Gsp1p-GTP complex (PDB code, 3WYG; Koyama et al 2014) with Ca r.m.s.d.…”

Section: Resultssupporting

confidence: 84%

“…2A-C), suggesting multivalent binding of the SxFG/ PxFG repeats to Xpo1p. Sites 2 and 3 were located on HEAT repeats 16-18 and HEAT repeats 14-15, respectively, and were not previously identified as FG repeat binding sites on Xpo1p in the Yrb2p complex (Koyama et al 2014). Sites 2 and 3 were located on HEAT repeats 16-18 and HEAT repeats 14-15, respectively, and were not previously identified as FG repeat binding sites on Xpo1p in the Yrb2p complex (Koyama et al 2014).…”

Section: Resultsmentioning

confidence: 80%

“…In the crystal structure of Xpo1p-PKI-Gsp1p-GTP complex, Gsp1p-GTP and the HEAT9 loop bind to the inner surface of HEAT repeats 15-19 and these interactions are abolished in the Xpo1p-Yrb1p-Gsp1p-GTP complex (Koyama & Matsuura 2010;Koyama et al 2014). In the crystal structure of Xpo1p-PKI-Gsp1p-GTP complex, Gsp1p-GTP and the HEAT9 loop bind to the inner surface of HEAT repeats 15-19 and these interactions are abolished in the Xpo1p-Yrb1p-Gsp1p-GTP complex (Koyama & Matsuura 2010;Koyama et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In the nucleus, Ran exists primarily in its GTP-bound state, because the chromatin-bound protein RCC1 (Prp20p in yeast), the guanine nucleotide exchange factor for Ran, is localized exclusively in the nucleus. The assembly of the CRM1-cargo-Ran-GTP complex (the CRM1 nuclear export complex) can be accelerated by a predominantly nuclear Ran-binding protein RanBP3 (Yrb2p in yeast) (Koyama et al 2014), which functions as a CRM1 (Xpo1p)-specific nuclear export cofactor (Taura et al 1998;Noguchi et al 1999;Englmeier et al 2001;Lindsay et al 2001). Consequently, Ran returns to the resting GDP-bound state in the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

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Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p

et al. 2017

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Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p

et al. 2017

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“…Furthermore, it is possible that other proteins play roles in the formation of the dots. The formation of RanGTP-XPO1-NES protein complexes is enhanced by Nup98 (64) and RanBP3 (65)(66)(67). Nup214 functions as a scaffold for the recruitment of several nucleoporins, such as Nup88, Nup358, Nup62, and Nup98 (38,40,68,69).…”

Section: Discussionmentioning

confidence: 99%

Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway

Saito

Cigdem

Okuwaki

et al. 2016

Molecular and Cellular Biology

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c Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEKNup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-B signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-B-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IB, in the nucleus. These results suggest that SETNup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Biological macromolecules are transported between the nucleus and the cytoplasm in response to extracellular signals. Transport of molecules with a molecular mass greater than 40 kDa does not occur by simple diffusion but is generally facilitated by nuclear transport receptors (NTRs) through nuclear pore complexes (NPCs) embedded in the nuclear envelope (1-3). Controlled nuclear-cytoplasmic transport plays important roles in maintaining cellular integrity in eukaryotic cells. It is reported that aberrant subcellular localization of some proteins is associated with various cancer cases (4). p53 has nuclear localization signals (NLSs) and nuclear export signals (NESs), and the accumulation of p53 in the cytoplasm has been reported to be a prognostic indicator in cancer (5). The nuclear factor B (NF-B) transcription factor is observed mainly in the cytoplasm in normal cells, whereas in many cancer cells, it is localized largely in the nucleus (6).In addition to aberrant subcellular localization of proteins in cancer, mutations of genes encoding NTRs and NPC components are found in various types of cancer (7). Mutations of exportin-5 (XPO5) and exportin-1 (XPO1)/CRM1, members of export receptors (8-10), are found in solid cancer and leukemia, respectively. Four nucleoporins-Nup98, Nup214/CAN, Nup358/ RanBP2, and Tpr-have been reported to form chimeric proteins by chromosomal translocations mainly in leukemia (11-15). Nup214, located at the cytoplasmic filament of the NPC, interacts with NTRs to control macromolecular transport....

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Construction of A High‐Flux Protein Transport Channel Inspired by the Nuclear Pore Complex

et al. 2021

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Inspired by the nuclear pore complex (NPC), herein we have established a biomimetic high-flux protein delivery system via the ingenious introduction of pillar [5]arene-based host-guest system into one side of artificial hour-glass shaped nanochannel. With a transport flux of 660 lysozymes per minute, the system provides efficient high-flux protein transport at a rate which is significantly higher than that of an unmodified nanochannel and conventional bilateral symmetrical modified nanochannels. In view of these promising results, the use of artificial nanochannel to improve protein transport not only presents a new potential chemical model for biological research and better understanding of protein transport behavior in the living systems, but also provides a highflux protein transporter device, which may have applications in the design of protein drug release systems, protein separation systems and microfluidics in the near future.

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Structural Insights into How Yrb2p Accelerates the Assembly of the Xpo1p Nuclear Export Complex

Cited by 37 publications

References 46 publications

Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p

Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p

Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway

Construction of A High‐Flux Protein Transport Channel Inspired by the Nuclear Pore Complex

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