2fu5

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(New page: 200px<br /> <applet load="2fu5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fu5, resolution 2.00&Aring;" /> '''structure of Rab8 i...)
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[[Image:2fu5.gif|left|200px]]<br />
 
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<applet load="2fu5" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2fu5, resolution 2.00&Aring;" />
 
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'''structure of Rab8 in complex with MSS4'''<br />
 
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==Overview==
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==structure of Rab8 in complex with MSS4==
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Rab GTPases function as essential regulators of vesicle transport in, eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab, proteins associated with the exocytic pathway and to have, nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of, MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange, factor that forms a long-lived nucleotide-free complex with RabGTPase. In, contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of, magnitude more slowly than comparable complexes. The crystal structure of, the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the, Switch I and interswitch regions of Rab8, forming an intermolecular, beta-sheet. Complex formation results in dramatic structural changes of, the Rab8 molecule, leading to unfolding of the nucleotide-binding site and, surrounding structural elements, facilitating nucleotide release and, slowing its rebinding. Coupling of nucleotide exchange activity to a cycle, of GTPase unfolding and refolding represents a novel nucleotide exchange, mechanism.
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<StructureSection load='2fu5' size='340' side='right'caption='[[2fu5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fu5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FU5 FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fu5 OCA], [https://pdbe.org/2fu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fu5 RCSB], [https://www.ebi.ac.uk/pdbsum/2fu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fu5 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MSS4_HUMAN MSS4_HUMAN] Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1 and RAB3A, but is less active on these proteins than on the SEC4 protein. Might play a general role in vesicular transport.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fu/2fu5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2fu5 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Rab GTPases function as essential regulators of vesicle transport in eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab proteins associated with the exocytic pathway and to have nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange factor that forms a long-lived nucleotide-free complex with RabGTPase. In contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of magnitude more slowly than comparable complexes. The crystal structure of the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the Switch I and interswitch regions of Rab8, forming an intermolecular beta-sheet. Complex formation results in dramatic structural changes of the Rab8 molecule, leading to unfolding of the nucleotide-binding site and surrounding structural elements, facilitating nucleotide release and slowing its rebinding. Coupling of nucleotide exchange activity to a cycle of GTPase unfolding and refolding represents a novel nucleotide exchange mechanism.
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==About this Structure==
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Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4.,Itzen A, Pylypenko O, Goody RS, Alexandrov K, Rak A EMBO J. 2006 Apr 5;25(7):1445-55. Epub 2006 Mar 16. PMID:16541104<ref>PMID:16541104</ref>
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2FU5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN and BME as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FU5 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4., Itzen A, Pylypenko O, Goody RS, Alexandrov K, Rak A, EMBO J. 2006 Apr 5;25(7):1445-55. Epub 2006 Mar 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16541104 16541104]
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</div>
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<div class="pdbe-citations 2fu5" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Goody RS]]
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[[Category: Goody, R.S.]]
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[[Category: Itzen A]]
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[[Category: Itzen, A.]]
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[[Category: Pylypenko O]]
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[[Category: Pylypenko, O.]]
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[[Category: Rak A]]
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[[Category: Rak, A.]]
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[[Category: BME]]
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[[Category: ZN]]
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[[Category: gef:gtpase nucleotide free complex]]
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[[Category: mss4:rab8 protein complex]]
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[[Category: nucleotide exchange via unfolding of nucleotide binding region]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:10:19 2007''
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Current revision

structure of Rab8 in complex with MSS4

PDB ID 2fu5

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