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[[Image:2c7n.gif|left|200px]]<br /><applet load="2c7n" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2c7n, resolution 2.10&Aring;" />
'''HUMAN RABEX-5 RESIDUES 1-74 IN COMPLEX WITH UBIQUITIN'''<br />


==Overview==
==Human Rabex-5 residues 1-74 in complex with Ubiquitin==
<StructureSection load='2c7n' size='340' side='right'caption='[[2c7n]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2c7n]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C7N 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2c7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c7n OCA], [https://pdbe.org/2c7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c7n RCSB], [https://www.ebi.ac.uk/pdbsum/2c7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c7n 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/c7/2c7n_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=2c7n ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.


==About this Structure==
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.,Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958<ref>PMID:16499958</ref>
2C7N 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 <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+K'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C7N OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin., Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR, Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16499958 16499958]
</div>
<div class="pdbe-citations 2c7n" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Rab5 GDP/GTP exchange factor|Rab5 GDP/GTP exchange factor]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Confalioneri, S.]]
[[Category: Confalioneri S]]
[[Category: Fiore, P P.Di.]]
[[Category: Di Fiore PP]]
[[Category: Magri, L.]]
[[Category: Magri L]]
[[Category: Mapelli, M.]]
[[Category: Mapelli M]]
[[Category: Murachelli, A G.]]
[[Category: Murachelli AG]]
[[Category: Musacchio, A.]]
[[Category: Musacchio A]]
[[Category: Penengo, L.]]
[[Category: Penengo L]]
[[Category: Polo, S.]]
[[Category: Polo S]]
[[Category: Schneider, T R.]]
[[Category: Schneider TR]]
[[Category: ZN]]
[[Category: endocytosis]]
[[Category: nuclear protein]]
[[Category: polyprotein]]
[[Category: ubiquitin binding domain]]
[[Category: ubiquitin complex]]
[[Category: ubl conjugation]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:46 2008''

Latest revision as of 12:22, 9 May 2024

Human Rabex-5 residues 1-74 in complex with UbiquitinHuman Rabex-5 residues 1-74 in complex with Ubiquitin

Structural highlights

2c7n is a 12 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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

The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.

Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.,Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958[4]

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

See Also

References

  1. ↑ Horiuchi H, Lippe R, McBride HM, Rubino M, Woodman P, Stenmark H, Rybin V, Wilm M, Ashman K, Mann M, Zerial M. A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell. 1997 Sep 19;90(6):1149-59. PMID:9323142
  2. ↑ Lippe R, Miaczynska M, Rybin V, Runge A, Zerial M. Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex. Mol Biol Cell. 2001 Jul;12(7):2219-28. PMID:11452015
  3. ↑ Delprato A, Merithew E, Lambright DG. Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5. Cell. 2004 Sep 3;118(5):607-17. PMID:15339665 doi:10.1016/j.cell.2004.08.009
  4. ↑ Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958 doi:http://dx.doi.org/10.1016/j.cell.2006.02.020

2c7n, resolution 2.10Å

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