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3gj3

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Revision as of 05:23, 7 December 2018

Crystal structure of human RanGDP-Nup153ZnF2 complex

Structural highlights

3gj3 is a 2 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3ch5, 2gqe, 1byu, 3gj0, 3gj4, 3gj5, 3gj6, 3gj7, 3gj8
Gene:	RAN, ARA24, OK/SW-cl.81 (HUMAN), Nup153 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.^[5] ^[6] ^[7] ^[8] [NU153_RAT] Possible DNA-binding subunit of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The nuclear pore complex (NPC) resides in circular openings within the nuclear envelope and serves as the sole conduit to facilitate nucleocytoplasmic transport in eukaryotes. The asymmetric distribution of the small G protein Ran across the nuclear envelope regulates directionality of protein transport. Ran interacts with the NPC of metazoa via two asymmetrically localized components, Nup153 at the nuclear face and Nup358 at the cytoplasmic face. Both nucleoporins contain a stretch of distinct, Ran-binding zinc finger domains. Here, we present six crystal structures of Nup153-zinc fingers in complex with Ran and a 1.48 A crystal structure of RanGDP. Crystal engineering allowed us to obtain well diffracting crystals so that all ZnF-Ran complex structures are refined to high resolution. Each of the four zinc finger modules of Nup153 binds one Ran molecule in apparently non-allosteric fashion. The affinity is measurably higher for RanGDP than for RanGTP and varies modestly between the individual zinc fingers. By microcalorimetric and mutational analysis, we determined that one specific hydrogen bond accounts for most of the differences in the binding affinity of individual zinc fingers. Genomic analysis reveals that only in animals do NPCs contain Ran-binding zinc fingers. We speculate that these organisms evolved a mechanism to maintain a high local concentration of Ran at the vicinity of the NPC, using this zinc finger domain as a sink.

Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.,Partridge JR, Schwartz TU J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6. PMID:19505478^[9]

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

References

↑ 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
↑ Partridge JR, Schwartz TU. Crystallographic and biochemical analysis of the Ran-binding zinc finger domain. J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6. PMID:19505478 doi:10.1016/j.jmb.2009.06.011

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gj3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human RanGDP-Nup153ZnF2 complex==
 <StructureSection load='3gj3' size='340' side='right' caption='[[3gj3]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ch5|3ch5]], [[2gqe|2gqe]], [[1byu|1byu]], [[3gj0|3gj0]], [[3gj4|3gj4]], [[3gj5|3gj5]], [[3gj6|3gj6]], [[3gj7|3gj7]], [[3gj8|3gj8]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Nup153 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3gj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gj3 OCA], [http://pdbe.org/3gj3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gj3 RCSB], [http://www.ebi.ac.uk/pdbsum/3gj3 PDBsum]</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=3gj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gj3 OCA], [http://pdbe.org/3gj3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gj3 RCSB], [http://www.ebi.ac.uk/pdbsum/3gj3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gj3 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gj/3gj3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gj/3gj3_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 41: / Line 42: @@
 [[Category: Partridge, J R]]
 [[Category: Schwartz, T U]]
+[[Category: Acetylation]]
+[[Category: Cytoplasm]]
 [[Category: Dna-binding]]
 [[Category: G protein]]
@@ Line 55: / Line 58: @@
 [[Category: Nup153]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Protein transport]]
 [[Category: Ran]]
@@ Line 60: / Line 64: @@
 [[Category: Transport]]
 [[Category: Transport protein]]
+[[Category: Ubl conjugation]]
+[[Category: Zinc]]
 [[Category: Zinc finger]]
 [[Category: Zinc-finger]]

3gj3

From Proteopedia

Revision as of 05:23, 7 December 2018

Crystal structure of human RanGDP-Nup153ZnF2 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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