返回顶部显示 11 - 20 件，共 29 件产品CAT.#SizePriceCypExpress 2B6，10 克 CE2B6.1010.0 克 3,760.00 克 CypExpress 2B6，250 毫克 CE2B6.250250 毫克 225.00 美元 CypExpress 2C19，1.0 克 CE2C19.1 1.0 克 $500.00CypExpress 2C19, 10 克 CE2C19.1010.0 克 $3,760.00CypExpress 2C19, 250 mgCE2C19.250250 毫克$225.00CypExpress 2C9, 1.0 克CE2C9.11.0 克$500.00CypExpress 2C9, 10 克CE2C9.1010.0 克$3,760.00CypExpress 2C9, 250 毫克CE2C9.250250 毫克$ 225.00CypExpress 2D6，1.0 克 CE2D6.11.0 克 $500.00CypExpress 2D6，10 克 CE2D6.1010.0 克 $3,760.00分页首页« FirstPrevious page‹ PreviousPage1当前页2Page3Next pageNext ›Last pageLast »返回顶部显示 1 - 10 件，共 29 件产品CAT.#SizePriceCypExpress 19A1，1 克 CE19A1.1g1.0 克 465.00 克 CypExpress 19A1，10 克 CE19A1.1010.0 克 3,760.00 克 CypExpress 19A1，250 毫克 CE19A1。 250 毫克250 毫克$210.00CypExpress 1A1, 1.0 克 CE1A1.11.0 克$500.00CypExpress 1A1 , 10.0 克 CE1A1.1010.0 克 3,760.00 美元 CypExpress 1A1, 250 毫克 CE1A1.250250 毫克 225.00 美元 CypExpress 1A2, 1.0 克 CE1A2.11.0 克 500.00 美元 CypExpress 1A2, 10 克 CE1A2。 1010.0 克$3,760.00CypExpress 1A2, 250 毫克CE1A2.250250 毫克$225.00CypExpress 2B6, 1 克CE2B6.11.0克$500.00分页当前页1页2页3下一页下一页›最后一页最后»返回顶部 CypExpress 2B6，1 克 500.00 美元SKUCE2B6.1产品概述

CypExpress™ 2B6 是一种透化和稳定的干酵母粉制剂，含有重组人 CYP 2B6 和重组人 NADPH 氧化还原酶。它专为快速筛选药物代谢物和扩大代谢物分离而设计​​。也提供 10.0 克规格和 250 毫克规格。批量订购请联系我们。

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产品文档MSDS CE2B6.1 SDSSpec Sheet CE2B6.1.160915相关产品ProductCAT.#SizePriceCypExpress 2B6, 250 mgCE2B6.250250 mg$225.00CypExpress 2E1, 250 mgCE2E1.250250 mg $225.00 CypExpress 19A1, 250 毫克CE19A1.250mg250 毫克$210.00CypExpress 1A1, 10.0 克CE1A1.1010.0 克$3,760.00CypExpress 1A1, 250 毫克CE1A1.250250 毫克$225.00返回顶部 CypExpress 1A1，10.0 克 3,760.00 美元SKUCE1A1.10产品概述

CypExpress™ 1A1 是一种透化和稳定的干酵母粉制剂，含有全长、未修饰的人 CYP 1A1 和重组人 P450 NADPH 氧化还原酶。它专为快速筛选药物代谢物和扩大代谢物生成而设计。也提供 1.0 克规格和 250 毫克规格。

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产品文档MSDS CE1A1.10 SDSSpec Sheet CE1A1.10.160502 SpecRelated ProductsProductCAT.#SizePriceCypExpress 19A1, 250 mgCE19A1.250mg250 mg$210.00CypExpress 1A1, 1.0 GramCE1A1.11。 0克500.00 美元 CypExpress 2B6，1 克 CE2B6.11.0 克 500.00 美元 CypExpress 2E1，250 毫克 CE2E1.250250 毫克 225.00 美元 CypExpress 2E1，10.0 克 CE2E1.1010.0 克 3,760.00 美元返回顶部 CypExpress 1A1，1.0 克 $500.00SKUCE1A1.1产品概述

CypExpress™ 1A1 是一种透化和稳定的干酵母粉制剂，含有全长、未修饰的人 CYP 1A1 和重组人 P450 NADPH 氧化还原酶。它专为快速筛选药物代谢物和扩大代谢物生成而设计。也提供 10.0 克规格和 250 毫克规格。

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CypExpress 应用

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CypExpress 系统

产品文档MSDS CE1A1.1 SDS Spec Sheet CE1A1.1.160502 SpecRelated ProductsProductCAT.#SizePriceGST M1-1, Recombinant HumanGS650.1 mg$460.00GST A4-4,重组人GS640.1 mg$460.00GST M2-2，重组人GS660.1 mg$460.00Anti-Human GST P1-1GS720.1 mL$380.00Anti-Human GST M1-1GS670.1 mL$380.00返回顶部 CypExpress 19A1，250 mg$210.00SKUCE19A1.250mg产品概述

CypExpress™ 19A1，也称为芳香酶，是一种透化稳定的干酵母粉制剂，含有重组人 CYP 19A1 和重组人 NADPH 氧化还原酶。它专为快速筛选药物代谢物和扩大代谢物分离而设计​​。也提供 1.0 克规格。如需批量订购，请联系我们。

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产品文件MSDS CE19A1.SDS__1.pdfSpec Sheet CE19A1.250mg.160812.pdf相关产品ProductCAT.#SizePriceCypExpress 2D6, 1.0 GramCE2D6.11.0 Gram$500.00CypExpress Control, 1.0 GramCENull.11.0 Gram$250.00 CypExpress 2C19, 10 克 CE2C19.1010.0 克3,760.00 美元 CypExpress 1A2，250 毫克 CE1A2.250250 毫克 225.00 美元 GST A3-3，重组大鼠 GS330.1 毫克 460.00 美元返回顶部 CypExpress 19A1，1 克 465.00 美元SKUCE19A1.1g产品概述

CypExpress™ 19A1，也称为芳香酶，是一种透性和稳定的干酵母粉制剂，含有重组人 CYP 19A1 和重组人 NADPH 氧化还原酶。它专为快速筛选药物代谢物和扩大代谢物分离而设计​​。也提供 10.0 克规格。如需批量订购，请联系我们。

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代谢物生产方案

CypExpress 应用

CypExpress 系统

产品文件MSDS CE19A1.SDS_.pdf规格表 CE19A1.1g.160812.pdf相关产品ProductCAT.#SizePriceCypExpress 2B6, 1 GramCE2B6.11.0 Gram$500.00CUPRACFood and Beverage Antioxidant AssayFS021 Kit$395.00CypExpress 1A1, 1.0 克 CE1A1.11.0 克 $500.00CypExpress 2C9，250 毫克 CE2C9.250250 毫克 $225.00CypExpress 2C19，1.0 克 CE2C19.11.0 克 $500.00返回顶部显示第 1 - 2 件，共 2 件产品CAT.#SizePriceNADPH-P450 还原酶，重组人 PH510.2 mg$390.00Recombinant Human Cytochrome b5PH91100 ug$420.00返回顶部显示第 1 - 2 件，共 2 件产品CAT.#SizePriceAnti-Rabbit Cytochrome b5PR910.1 mL$275.00Recombinant Human Cytochrome b5PH91100 ug$420.00返回顶部显示 1 - 4 件，共 4 件产品CAT.#SizePriceAnti-Human CYP450 3A4，Rabbit PolyclonalPA320.1 mL$315.00Anti-Rat CYP450 3A1，MonoclonalPM400.1 mL$360.00KetoconazoleX3250 mg$85.00Oxidized NifedipineX305 mg$ 225.00返回顶部显示第 1 - 4 件，共 4 件产品CAT.#SizePriceAnti Rabbit CYP450 2E1PR320.1 mL$280.00Anti-Human CYP450 2E1, Rabbit PolyclonalPA260.1 mL$315.00Anti-Rat CYP450 2E1, MonoclonalPM320.1 mL$360.00CY P450 1A1/1A2 免疫前山羊血清PR31c1.0毫升 $110.00返回顶部显示 1 - 1 件，共 1 件产品CAT.#SizePriceAnti-Human CYP450 2D6, Goat PolyclonalPA450.1 mL$310.00返回顶部显示 1 - 1 件，共 1 件产品CAT.#SizePriceAnti-Human CYP450 2C10, Rabbit PolyclonalPA220.1 mg$315.00 The classic nuclear protein import cycle functions as a biological molecular ratchet and is powered by the Ran GTPase that modulates interactions between carrier molecules and their cargoes. In the cytoplasm, cargo molecules carrying a classic nuclear localization signal (NLS) sequence are attached to the carrier importin-尾 by the importin-伪 adaptor. Cargoes are released in the nucleus following RanGTP binding to importin-尾, after which the importins are recycled. Nuclear pores facilitate the equilibration of cargo:carrier complexes between the nucleus and the cytoplasm. Transport directionality is imposed by import-complex dissociation by RanGTP in the nucleus and by RanGTP hydrolysis in the cytoplasm. Energy is used to orchestrate the binding and release of cargoes in the appropriate compartments rather than to move material directly through the pores. Movement of material backwards and forwards through nuclear pores is facilitated by interactions with nuclear pore proteins (nucleoporins) that contain Phe-Gly (FG) sequence repeats. These proteins also obstruct the passage of proteins that lack an NLS. Nucleoporins on the nuclear face of the NPC accelerate import-complex disassembly and provide a molecular ratchet to prevent futile cycles in which cargo is returned to the cytoplasm. Molecular flexibility is important in modulating interactions between importins and their partners. AbstractThe nuclear import of proteins through nuclear pore complexes (NPCs) illustrates how a complex biological function can be generated by a spatially and temporally organized cycle of interactions between cargoes, carriers and the Ran GTPase. Recent work has given considerable insight into this process, especially about how interactions are coordinated and the basis for the molecular recognition that underlies the process. Although considerable progress has been made in identifying and characterizing the molecular interactions in the soluble phase that drive the nuclear protein import cycle, understanding the precise mechanism of translocation through NPCs remains a major challenge. Subscription info for Chinese customersWe have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.Go to naturechina.comRent or Buy articleGet time limited or full article access on ReadCube.from$8.99Rent or BuyAll prices are NET prices. References1G枚rlich, D. Kutay, U. Transport between the cell nucleus and the cytoplasm. Ann. Rev. Cell Dev. Biol. 15, 607鈥?60 (1999).ArticleGoogle Scholar 2Macara, I. G. Transport into and out of the nucleus. Microbiol. Mol. Biol. Rev. 65, 570鈥?94 (2001).Article CAS PubMed PubMed CentralGoogle Scholar 3Chook, Y. M. Blobel, G. Karyopherins and nuclear import. Curr. Opin. Struct. Biol. 11, 703鈥?15 (2001).Article CAS PubMedGoogle Scholar 4Conti, E. Izaurralde, E. Nuclear transport enters the atomic age. Curr. Opin. Cell Biol. 13, 310鈥?19 (2001).Article CAS PubMedGoogle Scholar 5Fahrenkrog, B. Aebi, U. The nuclear pore complex: nucleocytoplasmic transport and beyond. Nature Rev. Mol. Cell Biol. 4, 757鈥?66 (2003).Article CASGoogle Scholar 6Mosammaparast, N. Pemberton, L. F. Karyopherins: from nuclear-transport mediators to nuclear-function regulators. Trends Cell Biol. 14, 547鈥?56 (2004).Article CAS PubMedGoogle Scholar 7Pemberton, L. F. Paschal, B. M. Mechanisms of receptor-mediated nuclear import and nuclear export. Traffic 6, 187鈥?98 (2005).Article CAS PubMedGoogle Scholar 8Madrid, A. S. Weis, K. Nuclear transport is becoming crystal clear. Chromosoma 115, 98鈥?09 (2006).Article PubMedGoogle Scholar 9Conti, E., M眉ller, C. W. Stewart, M. Karyopherin flexibility in nucleocytoplasmic transport. Curr. Opin. Struct. Biol. 16, 237鈥?44 (2006).Article CAS PubMedGoogle Scholar 10Stewart, M. et al. Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import. FEBS Lett. 498, 145鈥?49 (2001).Article CAS PubMedGoogle Scholar 11Weis, K. Regulating access to the genome. Nucleocytoplasmic transport throughout the cell cycle. Cell 112, 441鈥?51 (2003).Article CASGoogle Scholar 12Feldherr, C. M., Akin, D. Cohen, R. J. Regulation of functional nuclear pores size in fibroblasts. J. Cell Sci. 114, 4621鈥?627 (2001).CAS PubMedGoogle Scholar 13Rout, M. P. Wente, S. R. Pores for thought: nuclear pore complex proteins. Trends Cell Biol. 4, 357鈥?65 (1994).Article CAS PubMedGoogle Scholar 14Rout, M. P. et al. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148, 635鈥?51 (2000). A landmark paper that established the complete protein composition of yeast NPCs together with the location of each nucleoporin as determined by electron microscopy. The authors also proposed an entropic gating mechanism to prevent entry of inappropriate material into the NPC transport channel.Article CAS PubMed PubMed CentralGoogle Scholar 15Cronshaw, J. M., Krutchinsky, A. N., Zhang, W., Chait, B. T. Matunis, M. J. Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 158, 915鈥?27 (2002).Article CAS PubMed PubMed CentralGoogle Scholar 16Timney, B. L. et al. Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo. J. Cell Biol. 175, 579鈥?93 (2006).Article CAS PubMed PubMed CentralGoogle Scholar 17Mosammaparast, N. et al. Nuclear import of histone H2A and H2B is mediated by a network of karyopherins. J. Cell Biol. 153, 251鈥?62 (2001).Article CAS PubMed PubMed CentralGoogle Scholar 18Lee, B. J. et al. Rules for nuclear localization sequence recognition by karyopherin尾2. Cell 126, 543鈥?58 (2006).Article CAS PubMed PubMed CentralGoogle Scholar 19Ribbeck, K. G枚rlich, D. Kinetic analysis of translocation through nuclear pore complexes. EMBO J. 20, 1320鈥?330 (2001). Presents a careful analysis of nuclear protein import kinetics and proposes a selective phase model based on the formation of a hydrogel formed by interactions between the hydrophobic cores of FG repeats.Article CAS PubMed PubMed CentralGoogle Scholar 20Ribbeck, K., Lipowsky, G., Kent, H. M., Stewart, M. G枚rlich, D. NTF2 mediates nuclear import of Ran. EMBO J. 17, 6587鈥?598 (1998).Article CAS PubMed PubMed CentralGoogle Scholar 21Smith, A. E., Brownawell, A. Macara, I. G. Nuclear import of Ran is mediated by the transport factor NTF2. Curr. Biol. 8, 1403鈥?406 (1998).Article CAS PubMedGoogle Scholar 22Conti, E., Uy, M., Leighton, L., Blobel, G. Kuriyan, J. Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin-伪. Cell 94, 193鈥?04 (1998). Pioneering determination of the structure of yeast importin-伪 and the way in which it binds NLSs.Article CAS PubMedGoogle Scholar 23Conti, E. Kuriyan, J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin-伪. Structure Fold. Des. 8, 329鈥?38 (2000).Article CAS PubMedGoogle Scholar 24Fontes, M. R., The, T. Kobe, B. Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-伪. J. Mol. Biol. 297, 1183鈥?194 (2000).Article CAS PubMedGoogle Scholar 25Hodel, M. R., Corbett, A. H. Hodel, A. E. Dissection of a nuclear localization signal. J. Biol. Chem. 276, 1317鈥?325 (2001).Article CAS PubMedGoogle Scholar 26Catimel, B. et al. Biophysical characterization of interactions involving importin-伪 during nuclear import. J. Biol. Chem. 276, 34189鈥?4198 (2001).Article CAS PubMedGoogle Scholar 27Rodriguez, M. et al. A cytotoxic ribonuclease variant with a discontinuous nuclear localization signal constituted by basic residues scattered over three areas of the molecule. J. Mol. Biol. 360, 548鈥?57 (2006).Article CAS PubMedGoogle Scholar 28Lee, S. J. et al. The structure of importin-尾 bound to SREBP-2: nuclear import of a transcription factor. Science 302, 1571鈥?575 (2003).Article CAS PubMedGoogle Scholar 29Cingolani, G., Bednenko, J., Gillespie, M. T. Gerace, L. Molecular basis for the recognition of a nonclassical nuclear localization signal by importin 尾. Mol. Cell 10, 1345鈥?353 (2002).Article CAS PubMedGoogle Scholar 30G枚rlich, D., Henklein, P., Laskey, R. A. Hartmann, E. A 41 amino acid motif in importin-伪 confers binding to importin-尾 and hence transit into the nucleus. EMBO J. 15, 1810鈥?817 (1996).Article PubMed PubMed CentralGoogle Scholar 31Weis, K., Ryder, U. Lamond, A. I. The conserved amino-terminal domain of hSRP1 伪 is essential for nuclear protein import. EMBO J. 15, 1818鈥?825 (1996).Article CAS PubMed PubMed CentralGoogle Scholar 32Kobe, B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin 伪. Nature Struct. Biol. 6, 388鈥?97 (1999). Pioneering structural paper that proposed how the importin-伪 IBB domain could have an autoinhibitory function that facilitates cargo release in the nucleus.Article CAS PubMedGoogle Scholar 33Matsuura, Y. Stewart, M. Structural basis for the assembly of a nuclear export complex. Nature 432, 872鈥?77 (2004). Describes the structure of the yeast CAS:RanGTP:importin-伪 complex, showing the central role of the IBB domain in preventing futile cycles in which cargo is returned to the cytoplasm. Also proposes a spring-loaded model to account for how karyopherin flexibility can mediate the release of importin-伪 following GTP hydrolysis on Ran.Article CAS PubMedGoogle Scholar 34Matsuura, Y., Lange, A., Harreman, M. T., Corbett, A. H. Stewart, M. Structural basis for Nup2p function in cargo release and karyopherin recycling in nuclear import. EMBO J. 22, 5358鈥?369 (2003).Article CAS PubMed PubMed CentralGoogle Scholar 35Matsuura, Y. Stewart, M. Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling. EMBO J. 24, 3681鈥?689 (2005). Demonstration of active displacement of cargo from importin-伪 by NUP50 and how this can generate a molecular ratchet to prevent futile cycles.Article CAS PubMed PubMed CentralGoogle Scholar 36Goldfarb, D. S., Corbett, A. H., Mason, D. A., Harreman, M. T. Adam, S. A. Importin 伪: a multi-purpose nuclear receptor. Trends Cell Biol. 14, 505鈥?14 (2004).Article CAS PubMedGoogle Scholar 37Hodel, H. E. et al. Nuclear localization signal-receptor affinity correlates with in vivo localization in S. cerevisiae. J. Biol. Chem. 281, 23545鈥?3556 (2006).Article CAS PubMedGoogle Scholar 38Yang, W., Gelles, J. Musser, S. M. Imaging of single-molecule translocation through nuclear pore complexes. Proc. Natl Acad. Sci. USA 101, 12887鈥?2892 (2004). Direct demonstration of the random-walk diffusion of import complexes in the central transport channel of NPCs.Article CAS PubMedGoogle Scholar 39Kubitscheck, U. et al. Nuclear transport of single molecules: dwell times at the nuclear pore complex. J. Cell Biol. 168, 233鈥?43 (2005).Article CAS PubMed PubMed CentralGoogle Scholar 40Wang, W. Musser, S. M. Nuclear import time and transport efficiency depend on importin 尾 concentration. J. Cell Biol. 174, 951鈥?61 (2006).Article CASGoogle Scholar 41Bayliss, R. et al. Interaction between NTF2 and xFxFG nucleoporins is required for the nuclear import of RanGDP. J. Mol. Biol. 293, 579鈥?93 (1999).Article CAS PubMedGoogle Scholar 42Bayliss, R., Littlewood, T. Stewart, M. Structural basis for the interaction between FxFG nucleoporin repeats and importin-尾 in nuclear trafficking. Cell 102, 99鈥?08 (2000). Describes the structural basis for the interaction between importin-尾 and FG-nucleoporin cores.Article CAS PubMedGoogle Scholar 43Bayliss, R., Littlewood, T., Strawn, L. A., Wente, S. R. Stewart, M. GLFG and FxFG nucleoporins bind to overlapping sites on importin-尾. J. Biol. Chem. 277, 50597鈥?0606 (2002).Article CAS PubMedGoogle Scholar 44Bayliss, R. et al. Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats. EMBO J. 21, 2843鈥?853 (2002).Article CAS PubMed PubMed CentralGoogle Scholar 45Fribourg, S. Braun, I. C., Izaurralde, E. Conti, E. Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol. Cell 8, 645鈥?56 (2001).Article CASGoogle Scholar 46Grant, R. P., Neuhaus, D. N. Stewart, M. Structural basis for the interaction between the Tap/NXF1 UBA domain and FG nucleoporins at 1脜 resolution. J. Mol. Biol. 326, 849鈥?58 (2003).Article CAS PubMedGoogle Scholar 47Rexach, M. Blobel, G. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 83, 683鈥?92 (1995).Article CAS PubMedGoogle Scholar 48Ribbeck, K. G枚rlich, D. The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion. EMBO J. 21, 2664鈥?671 (2002).Article CAS PubMed PubMed CentralGoogle Scholar 49Strawn, L. A., Shen, T. Wente, S. R. The GLFG regions of Nup116p and Nup100p serve as binding sites for both Kap95p and Mex67p at the nuclear pore complex. J. Biol. Chem. 276, 6445鈥?452 (2001).Article CAS PubMedGoogle Scholar 50Strawn, L. A., Shen, T., Shulga, N., Goldfarb, D. S. Wente, S. R. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nature Cell Biol. 6, 197鈥?06 (2004). Exploration of the importance of the FG-repeat regions of nucleoporins using an innovative method for deleting these regions in S. cerevisiae . Whereas up to half the mass of FG repeats can be deleted using particular groups of nucleoporins, deletion from several selected nucleoporins has a marked effect.Article CAS PubMedGoogle Scholar 51Tran, E. J. Wente, S. R. Dynamic nuclear pore complexes: life on the edge. Cell 125, 1041鈥?053 (2006).Article CAS PubMedGoogle Scholar 52Grote, M., Kubitscheck, U., Reichelt, R. Peters, R. Mapping of nucleoporins to the centre of the nuclear pore complex by post-embedding immunogold electron microscopy. J. Cell Sci. 108, 2963鈥?972 (1995).CAS PubMedGoogle Scholar 53Denning, D. P., Uversky, V., Patel, S. S., Fink, A. L. Rexach, M. The Saccharomyces cerevisiae nucleoporin Nup2p is a natively unfolded protein. J. Biol. Chem. 277, 33447鈥?3455 (2002).Article CAS PubMedGoogle Scholar 54Denning, D. P., Patel, S. S., Uversky, V., Fink, A. L. Rexach, M. Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc. Natl Acad. Sci. USA 100, 2450鈥?455 (2003).Article CAS PubMedGoogle Scholar 55Paulillo, S. M. et al. Nucleoporin domain topology is linked to transport status of the nuclear pore complex. J. Mol. Biol. 351, 784鈥?98 (2005).Article CAS PubMedGoogle Scholar 56Liu, S. M. Stewart, M. Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-尾 homologue, Kap95p. J. Mol. Biol. 349, 515鈥?25 (2005).Article CAS PubMedGoogle Scholar 57Bednenko, J., Cingolani, G. Gerace, L. Importin 尾 contains a COOH-terminal nucleoporin binding region important for nuclear transport. J. Cell Biol. 162, 391鈥?01 (2003).Article CAS PubMed PubMed CentralGoogle Scholar 58Ben-Efraim, I. Gerace, L. Gradient of increasing affinity of importin-尾 for nucleoporins along the pathway of nuclear import. J. Cell Biol. 152, 411鈥?18 (2001).Article CAS PubMed PubMed CentralGoogle Scholar 59Pyhtila, B. Rexach, M. A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex. J. Biol. Chem. 278, 42699鈥?2709 (2003).Article CAS PubMedGoogle Scholar 60Zeitler, B. Weis, K. The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk nucleocytoplasmic transport in vivo. J. Cell Biol. 167, 583鈥?90 (2004).Article CAS PubMed PubMed CentralGoogle Scholar 61Nachury, M. V. Weis, K. The direction of transport through the nuclear pore can be inverted. Proc. Natl Acad. Sci. USA 96, 9622鈥?627 (1999). Direct demonstration that the directionality of nuclear transport can be reversed by reversing the RanGTP gradient. This work shows conclusively that directionality of transport is driven by the Ran nucleotide state and not by a nucleoporin-affinity gradient for importin-尾.Article CAS PubMedGoogle Scholar 62Lim, R. Y. et al. Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc. Natl Acad. Sci. USA 103, 9512鈥?517 (2006). This paper uses atomic force microscopy to show that FG-repeats can form molecular brushes when bound to gold particles in vitro.Article CAS PubMedGoogle Scholar 63Rout, M. P., Aitchison, J. D., Magnasco, M. O. Chait, B. T. Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622鈥?28 (2003).Article CAS PubMedGoogle Scholar 64Tanford, C. The Physical Chemistry of Macromolecules. (Wiley, New York, 1961). Google Scholar 65de Gennes, P. G. Conformations of polymers attached to an interface. Macromolecules 13, 1069鈥?075 (1980).Article CASGoogle Scholar 66Frey, S., Richter, R. P. G枚rlich, D. FG-rich repeats of nuclear pore proteins form a three-dimensional meshwork with hydrogel-like properties. Science 314, 815鈥?17 (2006).Article CASGoogle Scholar 67Doi, M. Edwards, S. F. The Theory of Polymer Dynamics (Oxford University Press, Oxford, 1986). Google Scholar 68Gilchrist, D., Mykytka, B. Rexach, M. Accelerating the rate of disassembly of karyopherin鈥揷argo complexes. J. Biol. Chem. 277, 18161鈥?8172 (2002).Article CAS PubMedGoogle Scholar 69Franke, W. W. Structure, biochemistry and functions of the nuclear envelope. Internat. Rev. Cytol. (Suppl. 4), 71鈥?36 (1974).70Richardson, W. D., Mills, A. D., Dilworth, S. M., Laskey, R. A. Dingwall, C. Nuclear protein migration involves two steps: rapid binding at the nuclear envelope followed by slower translocation through nuclear pores. Cell 52, 655鈥?64 (1988).Article CAS PubMedGoogle Scholar 71Walther, T. C. et al. The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J. Cell Biol. 158, 63鈥?7 (2002).Article CAS PubMed PubMed CentralGoogle Scholar 72Rexach, M. Blobel, G. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors and nucleoporins. Cell 83, 683鈥?92 (1995).Article CAS PubMedGoogle Scholar 73Vetter, I. R., Arndt, A., Kutay, U., G枚rlich, D. Wittinghofer, A. Structural view of the Ran-importin 尾 interaction at 2. 3 脜 resolution. Cell 97, 635鈥?46 (1999).Article CAS PubMedGoogle Scholar 74Lee, S. J., Matsuura, Y., Liu, S. M. Stewart, M. Structural basis for nuclear import complex dissociation by RanGTP. Nature 435, 693鈥?96 (2005). The structure of full-length yeast importin-尾 bound to RanGTP shows how Ran binding alters the pitch of the importin-尾 helicoid and facilitates release of the importin-伪 IBB domain.Article CAS PubMedGoogle Scholar 75Cingolani, G., Petosa, C., Weis, K. M眉ller C. W. Structure of importin-尾 bound to the IBB domain of importin-伪. Nature 399, 221鈥?29 (1999). Structure of the IBB:importin-尾 complex showing how the 19 HEAT repeats of importin-尾 are arranged to form a helicoidal molecule that coils around the 伪-helical IBB domain. Comparison between different crystal forms indicated that importin-尾 might be flexible.Article CAS PubMedGoogle Scholar 76G枚rlich, D. et al. A novel class of RanGTP binding proteins. J. Cell Biol. 138, 65鈥?0 (1997).Article PubMed PubMed CentralGoogle Scholar 77Chook, Y. M. Blobel, G. Structure of the nuclear transport complex karyopherin-尾2鈥揜an x GppNHp. Nature 399, 230鈥?37 (1999).Article CAS PubMedGoogle Scholar 78Bischoff, F. R. G枚rlich, D. RanBP1 is crucial for the release of RanGTP from importin-尾-related nuclear transport factors. FEBS Lett. 419, 249鈥?54 (1997).Article CAS PubMedGoogle Scholar 79Cook, A. et al. The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding. Mol. Cell 18, 355鈥?67 (2005). Direct demonstration of the dramatic conformational change in the yeast homologue of CAS, Cse1. In the absence of RanGTP and importin-伪, the Cse1 helicoid adopts a closed conformation in which the N terminus becomes bound to a region near the centre of the molecule.Article CAS PubMedGoogle Scholar 80Fukuhara, N., Fernandez, E., Ebert, J., Conti, E. Svergun, D. Conformational variability of nucleo-cytoplasmic transport factors. J. Biol. Chem. 279, 2176鈥?181 (2004). Low-angle X-ray scattering is used to show that several 尾-karyopherins can adopt different structures in solution, leading to the concept of these molecules having flexible structures.Article CAS PubMedGoogle Scholar 81Stewart, M. Molecular recognition in nuclear trafficking. Science 302, 1513鈥?514 (2003).Article CAS PubMedGoogle Scholar 82G枚rlich, D., Seewald, M. J. Ribbeck, K. Characterization of Ran-driven cargo transport and the RanGTPase system by kinetic measurements and computer simulation. EMBO J. 22, 1088鈥?100 (2003).Article PubMed PubMed CentralGoogle Scholar 83Riddick, G. Macara, I. G. A systems analysis of importin-伪:尾 mediated nuclear protein import. J. Cell Biol. 168, 1027鈥?038 (2005). A comprehensive simulation of the classic nuclear protein import cycle that gives several novel and unanticipated functional insights.Article CAS PubMed PubMed CentralGoogle Scholar 84Smith, A., Slepchenko, B. M., Schaff, J. C. Loew, L. M. Macara, I. G. Systems analysis of Ran transport. Science 295, 488鈥?91 (2002).Article CAS PubMedGoogle Scholar 85Becskei, A. Mattaj, I. W. Quantitative models of nuclear transport. Curr. Opin. Cell Biol. 17, 27鈥?4 (2005).Article CAS PubMedGoogle Scholar 86Akey, C. W. Structural plasticity of the nuclear pore complex. J. Mol. Biol. 248, 273鈥?93 (1995).CAS PubMedGoogle Scholar 87Akey, C. W. Radermacher, M. Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy. J. Cell Biol. 122, 1鈥?9 (1993).Article CAS PubMedGoogle Scholar 88Stoffler, D. et al. Cryo-electron microscopy provides novel insights into nuclear pore architecture: implications for nucleocytoplasmic transport. J. Mol. Biol. 328, 119鈥?30 (2003). Comprehensive analysis of NPC morphology using cryo-EM and tomography.Article CAS PubMedGoogle Scholar 89Lim, R. Y. H. Fahrenkrog, B. The nuclear pore complex up close. Curr. Opin. Cell Biol. 18, 342鈥?47 (2006).Article CAS PubMedGoogle Scholar 90Lim, R. Y., Aebi U. Stoffler D. From the trap to the basket: getting to the bottom of the nuclear pore complex. Chromosoma 115, 15鈥?6 (2006).Article PubMedGoogle Scholar 91Beck, M. et al. Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306, 1387鈥?390 (2004).Article CAS PubMedGoogle Scholar 92Fahrenkrog, B. et al. Domain-specific antibodies reveal multiple-site topology of Nup153 within the nuclear pore complex. J. Struct. Biol. 140, 254鈥?67 (2002).Article CAS PubMedGoogle Scholar 93Devos, D. et al. Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PloS Biol. 2, e380 (2004).Article CAS PubMed PubMed CentralGoogle Scholar 94Vetter, I. R., Nowak, C., Nishimoto, T., Kuhlmann, J. Wittinghofer, A. Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Nature 398, 39鈥?6 (1999).Article CAS PubMedGoogle Scholar 95Stewart, M., Kent, H. M. McCoy, A. J. Structural basis for molecular recognition between nuclear transport factor 2 (NTF2) and the GDP-bound form of the Ras-family GTPase, Ran. J. Mol. Biol. 277, 635鈥?46 (1998).Article CAS PubMedGoogle Scholar 96Bullock, T. L., Clarkson, W. D., Kent, H. M. Stewart, M. The 1.6 脜 resolution crystal structure of nuclear transport factor 2 (NTF2). J. Mol. Biol. 260, 422鈥?31 (1996).Article CAS PubMedGoogle Scholar 97Renault, L., Kuhlmann, J., Henkel, A. Wittinghofer, A. Structural basis for guanine nucleotide exchange on ran by the regulator of chromosome condensation (RCC1). Cell 105, 245鈥?55 (2001).Article CAS PubMedGoogle Scholar 98Hillig, R. C. et al. The crystal structure of rna1p: a new fold for a GTPase activating protein. Mol. Cell 3, 781鈥?91 (1999).Article CAS PubMedGoogle Scholar 99Seewald, M. J., Korner, C., Wittinghofer, A. Vetter, I. R. RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415, 662鈥?66 (2002).Article CAS PubMedGoogle Scholar Download referencesAuthor informationAffiliationsMRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UKMurray StewartAuthorsMurray StewartView author publicationsYou can also search for this author in PubMedGoogle ScholarEthics declarations Competing interests The author declares no competing financial interests. Supplementary informationSupplementary information S1 (movie)Structure of importin-a bound to the nucleoplasmin nuclear localization signal (NLS). Importin-伪 (green) is constructed from a tandem series of Armadillo (ARM) repeats that stack to form a gently curving banana-like molecule. NLSs (blue) bind to the inner concave surface. See also Figure 2b. (PDB accession number 1EYJ). (MOV 4209 kb)Supplementary information S2 (movie)Structure of importin-尾 complexed with the importin-伪 IBB (importin-尾 binding) domain. \'Importin-尾\' (cyan) is constructed from 19 tandem HEAT repeats, each of which contains two 伪-helices (See BOX 2). The HEAT repeats stack to form a helicoidal molecule that coils around the IBB domain 伪-helix (red) like a snake around its prey. (PDB accession number 1QGK). (MOV 8513 kb)Supplementary information S3 (movie)Structure of Ran showing the structural changes between the GDP- and GTP-bound states. The larger switch I and smaller switch II loops change conformation dramatically depending on the state of the bound nucleotide (GTPbound is red; GDP-bound is blue) and these changes control the way in which Ran interacts with its partners in the nuclear protein import pathway. The remainder of the Ran chain (shown as cyan for GTP-bound and yellow for GDP-bound) is virtually unchanged by the state of the bound nucleotide. (PDB accession files 1BYU (RanGDP) and 1RRP (RanGTP). Only residues 8-177 are shown. (MOV 6825 kb)Supplementary information S4 (movie)Conformational changes in importin-尾 between different functional states. Comparison of the structures of importin-尾 when bound to either the IBB domain (cyan) or RanGTP (yellow) shows the large conformational change that occurs between different functional states. When bound to RanGTP, the importin-尾 helicoid pitch increases dramatically so that it no longer matches the IBB domain\'s 伪-helix, thus leading to import complex disassembly (see also Figure 3c). IBB domain is red. (PDB accession codes 1QGK and 2BKU). (MOV 13233 kb)Supplementary information S5 (movie)Structure of the complex between yeast importin-尾 (Kap95p) and RanGTP. Importin-尾 (yellow) coils around RanGTP (cyan) interacting with it at three sites (see also Figure 3 a,b). GTP is shown in space-filling format. (PDB accession code 2BKU). (MOV 8743 kb)Supplementary information S6 (movie)Structure of the complex between Nup50 and importin-伪. The Nup50 Nterminus (blue) binds to two sites on importin-伪 (green): a higher affinity site at the importin-伪 C-terminus (at the top of the molecule in this movie) and a lower affinity site that overlaps the NLS binding area (in the central region of the importin-伪 chain). Nup50 binding actively displaces nuclear localization signals (NLSs) from importin-伪. (PDB accession code 2C1M). (MOV 3736 kb)Supplementary information S7 (movie)Structure of the CAS:importin-伪:RanGTP nuclear export complex. CAS (yeast Cse1, yellow) coils around both RanGTP (cyan) and importin-伪 (green) in the complex. The IBB domain (blue) is sandwiched between CAS and importin-伪. The binding of the IBB domain to the NLS binding sites is crucial for the formation of this complex and ensures that only cargo-free importin-伪 is exported to the nucleus, thus preventing futile transport cycles. (PDB accession code 1WA5). (MOV 9573 kb)Supplementary information S8 (movie)Structure of isolated CAS. Isolated CAS (cyan), corresponding to the species present in the cytoplasm after the export complex dissociates following RanGTP hydrolysis, assumes a \"closed\" conformation in which its N-terminus binds to a region near the centre of the molecule. (PDB accession code 1Z3H). (MOV 7422 kb)Supplementary information S9 (movie)Comparison between the open and closed forms of CAS. CAS undergoes a considerable conformational change between the open form assumed in the CAS:importin-伪:RanGTP export complex (yellow) and the closed form (cyan) that results from the disassembly of this complex in the cytoplasm following GTP hydrolysis on Ran. The helicoidal pitch has changed substantially between the two forms (compare with S4, movie), consistent with the molecule being flexible. (PDB accession codes 1Z3H and 1WA5). (MOV 10126 kb)Supplementary information S10 (movie)Illustration of the conformational change in CAS between the open and closed states. The MolMov package (http://bioinfo.mbb.yale.edu/MolMovDB) was used to simulate the transition between the \"open\" and \"closed\" forms of CAS. (PDB accession codes 1Z3H and 1WA5). (MOV 3809 kb)Supplementary information S11 (movie)Structure of nuclear transport factor 2 (NTF2). NTF2 is a dimer constructed from two chains (cyan and yellow). Each chain generates a hydrophobic cavity to which RanGDP binds (see S12, movie), whereas a hydrophobic patch formed between the two NTF2 chains binds the FxFG repeats from nucleoporins. (PDB accession number 1GY6). (MOV 8015 kb)Supplementary information S12 (movie)Complex between nuclear transport factor 2 (NTF2) and RanGDP. Two RanGDP chains (red and yellow) bind to the hyrodophobic cavities in the NTF2 dimer (blue and cyan) to facilitate its transport into the nucleus for nucleotide exchange using RanGEF. GDP is shown as space-filling format. (PDB accession number 1A2K). (MOV 7023 kb)Supplementary information S13 (movie)Structure of the metazoan RanGEF, RCC1. RCC1 (cyan) is based on a seven-bladed propeller structure. It accelerates the rate of nucleotide exchange on Ran by stabilizing the nucleotide-free state. (PDB accession code 1A12). (MOV 3546 kb)Supplementary information S14 (movie)Structure of the yeast RanGAP, Rna1. RanGAP (green) is constructed from leucine-rich repeats (LLRs each based on an 伪-helix and a 尾-strand) and accelerates the rate of the Ran GTPase by 鈭?/span>105. (PDB accession code 2CA6). (MOV 4027 kb)Related linksRelated linksFURTHER INFORMATION Murray Stewart\'s homepage GlossaryCoiled coil A protein fold in which two 伪-helices coil around one another. WD propeller A protein fold formed by a series of repeating WD sequence motifs that structurally resemble the blades of a propeller. 伪-helical solenoid A protein fold formed by successive repeats, each of which contains a number of 伪-helices that form a loop that is like a coil of a spring or solenoid. Adaptor proteins Proteins that augment cellular responses by recruiting other proteins to a complex. They usually contain several protein:protein interaction domains. Scanning Ala mutagenesis A technique in which successive residues in a region of a sequence of a protein are mutated to Ala to define those that influence an activity, such as binding to another protein. Random walk The path followed by taking successive steps, each in a random direction relative to the previous step. Entropy The component of free energy due to the disorder or randomness of the system. Increases in entropy (disorder) lower the free energy, whereas increases in order (lower entropy) increase energy. Enthalpy The heat component of free energy that, in biological systems, is derived primarily from chemical bonds. Le Chatelier\'s principle Le Chatelier\'s principle states that if a dynamic equilibrium is disturbed by changing conditions, the position of equilibrium moves to counteract the change. Thermal ratchet A molecular mechanism by which the thermal (Brownian) motion of a particle is biased (or rectified) so that there is net movement in a particular direction. A thermal ratchet requires an input of energy in order not to violate the second law of thermodynamics. Helicoidal pitch The distance along the axis of a helicoid corresponding to a rotation of 360掳. Helicoid A spiral that is shaped like the shell of a snail such that its radius decreases progressively along its axis. Sensitivity analysis A procedure to determine the sensitivity of the outcomes of a model to changes in its parameters. Rights and permissionsReprints and PermissionsAbout this articleCite this articleStewart, M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol 8, 195鈥?08 (2007). https://doi.org/10.1038/nrm2114Download citationPublished: 07 February 2007Issue Date: March 2007DOI: https://doi.org/10.1038/nrm2114 Juane Lu, Tao Wu, Biao Zhang, Suke Liu, Wenjun Song, Jianjun Qiao Haihua Ruan Cell Communication and Signaling (2021) Tingting Chen, Jing Peng, Xiao Yin, Meijie Li, Gaoqing Xiang, Yuejin Wang, Yan Lei Yan Xu Horticulture Research (2021) Yisha Zhuo, Zeheng Guo, Tongtong Ba, Cheng Zhang, Lihua He, Cuiping Zeng Hanchuan Dai Virologica Sinica (2021) Zheng Zhu, Yang Lan, Lihong Wang, Jia Ge, Jiao Wang, Feng Liu, Zhicheng He, Hua Zhang, Min Luo, Dandan Lin, Yaoyao Tan, Yuanyuan Xu Tao Luo BMC Cancer (2020) Sign up for the Nature Briefing newsletter 鈥?what matters in science, free to your inbox daily.