1i2m: Difference between revisions

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New page: left|200px<br /> <applet load="1i2m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i2m, resolution 1.76Å" /> '''RAN-RCC1-SO4 COMPLE...
 
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[[Image:1i2m.gif|left|200px]]<br />
<applet load="1i2m" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1i2m, resolution 1.76&Aring;" />
'''RAN-RCC1-SO4 COMPLEX'''<br />


==Overview==
==RAN-RCC1-SO4 COMPLEX==
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.
<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 [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1I2M FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1i2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i2m OCA], [https://pdbe.org/1i2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i2m RCSB], [https://www.ebi.ac.uk/pdbsum/1i2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i2m ProSAT]</span></td></tr>
</table>
== Function ==
[https://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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i2/1i2m_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i2m ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==Disease==
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<ref>PMID:11336674</ref>
Known diseases associated with this structure: Alveolar soft-part sarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606236 606236]], Osteolysis, familial expansile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603499 603499]], Paget disease of bone OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603499 603499]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1I2M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I2M OCA].
</div>
<div class="pdbe-citations 1i2m" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11336674 11336674]
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Henkel, A.]]
[[Category: Henkel A]]
[[Category: Kuhlmann, J.]]
[[Category: Kuhlmann J]]
[[Category: Renault, L.]]
[[Category: Renault L]]
[[Category: Wittinghofer, A.]]
[[Category: Wittinghofer A]]
[[Category: SO4]]
[[Category: beta-propeller]]
[[Category: g fold or gtpase fold]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:25:37 2007''

Latest revision as of 09:20, 9 August 2023

RAN-RCC1-SO4 COMPLEXRAN-RCC1-SO4 COMPLEX

Structural highlights

1i2m is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.76Å
Ligands:
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]

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[9]

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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

1i2m, resolution 1.76Å

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