2ot3: Difference between revisions

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[[Image:2ot3.gif|left|200px]]
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{{STRUCTURE_2ot3|  PDB=2ot3  |  SCENE=  }}
'''Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21'''


==Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21==
<StructureSection load='2ot3' size='340' side='right'caption='[[2ot3]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ot3]] is a 2 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=2OT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OT3 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]] 2.1&#8491;</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=2ot3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ot3 OCA], [https://pdbe.org/2ot3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ot3 RCSB], [https://www.ebi.ac.uk/pdbsum/2ot3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ot3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RABX5_HUMAN RABX5_HUMAN] Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity).<ref>PMID:9323142</ref> <ref>PMID:11452015</ref> <ref>PMID:15339665</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/ot/2ot3_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=2ot3 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RABEX-5 and other exchange factors with VPS9 domains regulate endocytic trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22. Here we report the crystal structure of the RABEX-5 catalytic core in complex with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway. The structure reveals how VPS9 domain exchange factors recognize Rab GTPase substrates, accelerate GDP release and stabilize the nucleotide-free conformation. We further identify an autoinhibitory element in a predicted amphipathic helix located near the C terminus of the VPS9 domain. The autoinhibitory element overlaps with the binding site for the multivalent effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5. Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5.


==Overview==
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.,Delprato A, Lambright DG Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:17450153<ref>PMID:17450153</ref>
RABEX-5 and other exchange factors with VPS9 domains regulate endocytic trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22. Here we report the crystal structure of the RABEX-5 catalytic core in complex with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway. The structure reveals how VPS9 domain exchange factors recognize Rab GTPase substrates, accelerate GDP release and stabilize the nucleotide-free conformation. We further identify an autoinhibitory element in a predicted amphipathic helix located near the C terminus of the VPS9 domain. The autoinhibitory element overlaps with the binding site for the multivalent effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5. Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2OT3 is a [[Protein complex]] structure of sequences 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=2OT3 OCA].
</div>
<div class="pdbe-citations 2ot3" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for Rab GTPase activation by VPS9 domain exchange factors., Delprato A, Lambright DG, Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17450153 17450153]
*[[Rab5 GDP/GTP exchange factor|Rab5 GDP/GTP exchange factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Delprato, A.]]
[[Category: Delprato A]]
[[Category: Lambright, D.]]
[[Category: Lambright D]]
[[Category: Protein transport]]
[[Category: Rab21]]
[[Category: Rabex-5]]
[[Category: Vesicular traffic]]
[[Category: Vps9 domain]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 11:36:07 2008''
Retrieved from "https://proteopedia.org/2ot3"