6q82: Difference between revisions

Latest revision as of 09:10, 9 October 2024

Crystal structure of the biportin Pdr6 in complex with RanGTP

Structural highlights

6q82 is a 2 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.994Å
Ligands:	GTP, MG, MSE
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]

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^[5]

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:https://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:https://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:https://dx.doi.org/10.1128/MCB.01388-08
↑ 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:https://dx.doi.org/10.1083/jcb.201812093

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1073/pnas.0510516103

[3] 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:https://dx.doi.org/10.1002/yea.320070311

[4] 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:https://dx.doi.org/10.1128/MCB.01388-08

[5] 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:https://dx.doi.org/10.1083/jcb.201812093

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@@ Line 3: / Line 3: @@
 <StructureSection load='6q82' size='340' side='right'caption='[[6q82]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6q82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q82 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6q82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q82 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.994&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KAP122, PDR6, YGL016W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6q82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q82 OCA], [https://pdbe.org/6q82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q82 RCSB], [https://www.ebi.ac.uk/pdbsum/6q82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q82 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6q82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q82 OCA], [http://pdbe.org/6q82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q82 RCSB], [http://www.ebi.ac.uk/pdbsum/6q82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q82 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/KA122_YEAST 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.<ref>PMID:10525531</ref> <ref>PMID:16432237</ref> <ref>PMID:1882553</ref> <ref>PMID:18838542</ref>  [[http://www.uniprot.org/uniprot/RAN_HUMAN 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.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>   Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>
+[https://www.uniprot.org/uniprot/KA122_YEAST 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.<ref>PMID:10525531</ref> <ref>PMID:16432237</ref> <ref>PMID:1882553</ref> <ref>PMID:18838542</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 6q82" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Baker's yeast]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Aksu, M]]
+[[Category: Saccharomyces cerevisiae S288C]]
-[[Category: Gorlich, D]]
+[[Category: Aksu M]]
-[[Category: Trakhanov, S]]
+[[Category: Gorlich D]]
-[[Category: Vera-Rodriguez, A]]
+[[Category: Trakhanov S]]
-[[Category: Biportin]]
+[[Category: Vera-Rodriguez A]]
-[[Category: Gtpase]]
-[[Category: Importin-beta family]]
-[[Category: Nuclear transport]]
-[[Category: Protein transport]]

6q82: Difference between revisions

Latest revision as of 09:10, 9 October 2024

Crystal structure of the biportin Pdr6 in complex with RanGTP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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