1i2m

From Proteopedia

(Difference between revisions)

Revision as of 05:17, 11 September 2015

RAN-RCC1-SO4 COMPLEX

Structural highlights

1i2m is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1a12, 1byu, 1rrp
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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] [RCC1_HUMAN] Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP. Involved in the regulation of onset of chromosome condensation in the S phase. Binds both to the nucleosomes and double-stranded DNA. RCC1-Ran complex (together with other proteins) acts as a component of a signal transmission pathway that detects unreplicated DNA. Plays a key role in nucleo-cytoplasmic transport, mitosis and nuclear-envelope assembly.^[9]

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

RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bound protein, is the guanine nucleotide exchange factor (GEF) for the nuclear GTP binding protein Ran. We report here the 1.8 A crystal structure of a Ran*RCC1 complex in the absence of nucleotide, an intermediate in the multistep GEF reaction. In contrast to previous structures, the phosphate binding region of the nucleotide binding site is perturbed only marginally, possibly due to the presence of a polyvalent anion in the P loop. Biochemical experiments show that a sulfate ion stabilizes the Ran*RCC1 complex and inhibits dissociation by guanine nucleotides. Based on the available structural and biochemical evidence, we present a unified scenario for the GEF mechanism where interaction of the P loop lysine with an acidic residue is a crucial element for the overall reaction.

Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1).,Renault L, Kuhlmann J, Henkel A, Wittinghofer A Cell. 2001 Apr 20;105(2):245-55. PMID:11336674^[10]

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
↑ Bischoff FR, Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature. 1991 Nov 7;354(6348):80-2. PMID:1944575 doi:http://dx.doi.org/10.1038/354080a0
↑ Renault L, Kuhlmann J, Henkel A, Wittinghofer A. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell. 2001 Apr 20;105(2):245-55. PMID:11336674

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/1i2m"

@@ Line 2: / Line 2: @@
 <StructureSection load='1i2m' size='340' side='right' caption='[[1i2m]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1i2m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I2M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1i2m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I2M FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a12|1a12]], [[1byu|1byu]], [[1rrp|1rrp]]</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=1i2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i2m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1i2m RCSB], [http://www.ebi.ac.uk/pdbsum/1i2m 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=1i2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i2m OCA], [http://pdbe.org/1i2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i2m RCSB], [http://www.ebi.ac.uk/pdbsum/1i2m PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1i2m" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Henkel, A]]
 [[Category: Kuhlmann, J]]

1i2m

From Proteopedia

Revision as of 05:17, 11 September 2015

RAN-RCC1-SO4 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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