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5xzx

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Revision as of 07:02, 14 October 2020

Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3

Structural highlights

5xzx is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IMA3_HUMAN] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. [RANB3_HUMAN] Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP prevents binding of XPO1/CRM1 to the nuclear pore complex. Binds to CHC1/RCC1 and increases the guanine nucleotide exchange activity of CHC1/RCC1. Recruits XPO1/CRM1 to CHC1/RCC1 in a Ran-dependent manner. Negative regulator of TGF-beta signaling through interaction with the R-SMAD proteins, SMAD2 and SMAD3, and mediating their nuclear export.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of beta-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-alpha and, RanBP3 is imported more efficiently by importin-alpha3 than by other members of the importin-alpha family. Protein kinase signaling pathways control nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58, immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal region of RanBP3. Here we report the crystal structure of human importin-alpha3 bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that is necessary and sufficient for nuclear import. The structure reveals that RanBP3 binds to importin-alpha3 residues that are strictly conserved in all seven isoforms of human importin-alpha at the major NLS-binding site, indicating that the region of importin-alpha outside the NLS-binding site, possibly the autoinhibotory importin-beta1-binding domain, may be the key determinant for the preferential binding of RanBP3 to importin-alpha3. Computational docking simulation indicates that phosphorylation of RanBP3 at Ser58 could potentially stabilize the association of RanBP3 with importin-alpha through interactions between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic residues (Arg96 and Lys97 in importin-alpha3) on armadillo repeat 1 of importin-alpha.

Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3.,Koyama M, Matsuura Y Biochem Biophys Res Commun. 2017 Sep 23;491(3):609-613. doi:, 10.1016/j.bbrc.2017.07.155. Epub 2017 Jul 29. PMID:28760339^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mueller L, Cordes VC, Bischoff FR, Ponstingl H. Human RanBP3, a group of nuclear RanGTP binding proteins. FEBS Lett. 1998 May 15;427(3):330-6. PMID:9637251
↑ Englmeier L, Fornerod M, Bischoff FR, Petosa C, Mattaj IW, Kutay U. RanBP3 influences interactions between CRM1 and its nuclear protein export substrates. EMBO Rep. 2001 Oct;2(10):926-32. Epub 2001 Sep 24. PMID:11571268 doi:http://dx.doi.org/10.1093/embo-reports/kve200
↑ Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG. Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export. J Cell Biol. 2001 Jun 25;153(7):1391-402. PMID:11425870
↑ Nemergut ME, Lindsay ME, Brownawell AM, Macara IG. Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor. J Biol Chem. 2002 May 17;277(20):17385-8. Epub 2002 Apr 3. PMID:11932251 doi:http://dx.doi.org/10.1074/jbc.C100620200
↑ Dai F, Lin X, Chang C, Feng XH. Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling. Dev Cell. 2009 Mar;16(3):345-57. doi: 10.1016/j.devcel.2009.01.022. PMID:19289081 doi:10.1016/j.devcel.2009.01.022
↑ Koyama M, Matsuura Y. Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3. Biochem Biophys Res Commun. 2017 Sep 23;491(3):609-613. doi:, 10.1016/j.bbrc.2017.07.155. Epub 2017 Jul 29. PMID:28760339 doi:http://dx.doi.org/10.1016/j.bbrc.2017.07.155

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xzx"

Categories: Large Structures | Koyama, M | Matsuura, Y | Nuclear import | Transport protein

@@ Line 1: / Line 1: @@
 ==Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3==
-<StructureSection load='5xzx' size='340' side='right' caption='[[5xzx]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='5xzx' size='340' side='right'caption='[[5xzx]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xzx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XZX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xzx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XZX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XZX FirstGlance]. <br>
-</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=5xzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xzx OCA], [http://pdbe.org/5xzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xzx RCSB], [http://www.ebi.ac.uk/pdbsum/5xzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xzx ProSAT]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xzx OCA], [http://pdbe.org/5xzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xzx RCSB], [http://www.ebi.ac.uk/pdbsum/5xzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xzx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
 </div>
 <div class="pdbe-citations 5xzx" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Importin 3D structures|Importin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Koyama, M]]
 [[Category: Matsuura, Y]]
 [[Category: Nuclear import]]
 [[Category: Transport protein]]

5xzx

From Proteopedia

Revision as of 07:02, 14 October 2020

Crystal structure of importin-alpha3 bound to the nuclear localization signal of Ran-binding protein 3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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