| Structural highlights
6q84 is a 6 chain structure with sequence from Baker's yeast and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | KAP122, PDR6, YGL016W (Baker's yeast), RAN, ARA24, OK/SW-cl.81 (HUMAN), HYP2, TIF51A, YEL034W, SYGP-ORF21 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 PubMed
Importins 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.
References
- ↑ Titov AA, Blobel G. The karyopherin Kap122p/Pdr6p imports both subunits of the transcription factor IIA into the nucleus. J Cell Biol. 1999 Oct 18;147(2):235-46. PMID:10525531
- ↑ Zhang Z, An X, Yang K, Perlstein DL, Hicks L, Kelleher N, Stubbe J, Huang M. Nuclear localization of the Saccharomyces cerevisiae ribonucleotide reductase small subunit requires a karyopherin and a WD40 repeat protein. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1422-7. doi:, 10.1073/pnas.0510516103. Epub 2006 Jan 23. PMID:16432237 doi:http://dx.doi.org/10.1073/pnas.0510516103
- ↑ Chen WN, Balzi E, Capieaux E, Choder M, Goffeau A. The DNA sequencing of the 17 kb HindIII fragment spanning the LEU1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae reveals the PDR6 gene, a new member of the genetic network controlling pleiotropic drug resistance. Yeast. 1991 Apr;7(3):287-99. doi: 10.1002/yea.320070311. PMID:1882553 doi:http://dx.doi.org/10.1002/yea.320070311
- ↑ Wu X, Huang M. Dif1 controls subcellular localization of ribonucleotide reductase by mediating nuclear import of the R2 subunit. Mol Cell Biol. 2008 Dec;28(23):7156-67. doi: 10.1128/MCB.01388-08. Epub 2008 Oct , 6. PMID:18838542 doi:http://dx.doi.org/10.1128/MCB.01388-08
- ↑ Lee YB, Joe YA, Wolff EC, Dimitriadis EK, Park MH. Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor. Biochem J. 1999 May 15;340 ( Pt 1):273-81. PMID:10229683
- ↑ Zanelli CF, Valentini SR. Pkc1 acts through Zds1 and Gic1 to suppress growth and cell polarity defects of a yeast eIF5A mutant. Genetics. 2005 Dec;171(4):1571-81. Epub 2005 Sep 12. PMID:16157662 doi:http://dx.doi.org/genetics.105.048082
- ↑ Chatterjee I, Gross SR, Kinzy TG, Chen KY. Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive temperature reveals connections to actin cytoskeleton and cell cycle progression. Mol Genet Genomics. 2006 Mar;275(3):264-76. Epub 2006 Jan 12. PMID:16408210 doi:http://dx.doi.org/10.1007/s00438-005-0086-4
- ↑ Zanelli CF, Maragno AL, Gregio AP, Komili S, Pandolfi JR, Mestriner CA, Lustri WR, Valentini SR. eIF5A binds to translational machinery components and affects translation in yeast. Biochem Biophys Res Commun. 2006 Oct 6;348(4):1358-66. Epub 2006 Aug 7. PMID:16914118 doi:http://dx.doi.org/10.1016/j.bbrc.2006.07.195
- ↑ Gregio AP, Cano VP, Avaca JS, Valentini SR, Zanelli CF. eIF5A has a function in the elongation step of translation in yeast. Biochem Biophys Res Commun. 2009 Mar 20;380(4):785-90. Epub 2009 Jan 29. PMID:19338753 doi:http://dx.doi.org/S0006-291X(09)00203-4
- ↑ Saini P, Eyler DE, Green R, Dever TE. Hypusine-containing protein eIF5A promotes translation elongation. Nature. 2009 May 7;459(7243):118-21. PMID:19424157 doi:http://dx.doi.org/nature08034
- ↑ Benne R, Hershey JW. The mechanism of action of protein synthesis initiation factors from rabbit reticulocytes. J Biol Chem. 1978 May 10;253(9):3078-87. PMID:641056
- ↑ Kang HA, Hershey JW. Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae. J Biol Chem. 1994 Feb 11;269(6):3934-40. PMID:8307948
- ↑ Zuk D, Jacobson A. A single amino acid substitution in yeast eIF-5A results in mRNA stabilization. EMBO J. 1998 May 15;17(10):2914-25. PMID:9582285 doi:http://dx.doi.org/10.1093/emboj/17.10.2914
- ↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
- ↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
- ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
- ↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
- ↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
- ↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
- ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
- ↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
- ↑ Aksu M, Trakhanov S, Vera Rodriguez A, Gorlich D. Structural basis for the nuclear import and export functions of the biportin Pdr6/Kap122. J Cell Biol. 2019 Apr 25. pii: jcb.201812093. doi: 10.1083/jcb.201812093. PMID:31023722 doi:http://dx.doi.org/10.1083/jcb.201812093
|
