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==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]] 2.10Å' scene=''> | <StructureSection load='2ot3' size='340' side='right'caption='[[2ot3]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ot3]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2ot3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1txu|1txu]], [[1z0i|1z0i]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1txu|1txu]], [[1z0i|1z0i]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RABGEF1, RABEX5 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RABGEF1, RABEX5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB21, KIAA0118 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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> | </table> | ||
== Function == | == 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> [[https://www.uniprot.org/uniprot/RAB21_HUMAN RAB21_HUMAN]] Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general. As a result, may regulate cell adhesion and migration (By similarity). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis.<ref>PMID:18804435</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ot/2ot3_consurf.spt"</scriptWhenChecked> | <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> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2ot3" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2ot3" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Rab5 GDP/GTP exchange factor|Rab5 GDP/GTP exchange factor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Delprato, A]] | [[Category: Delprato, A]] | ||
[[Category: Lambright, D]] | [[Category: Lambright, D]] | ||
Revision as of 16:05, 9 June 2021
Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21
Structural highlights
Function[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).[1] [2] [3] [RAB21_HUMAN] Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general. As a result, may regulate cell adhesion and migration (By similarity). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis.[4] 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 PubMedRABEX-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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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