4n3x: Difference between revisions

Revision as of 10:31, 28 December 2022

Crystal structure of Rabex-5 CC domain

Structural highlights

4n3x 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.
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]

Publication Abstract from PubMed

Rabex-5 and Rabaptin-5 function together to activate Rab5 and further promote early endosomal fusion in endocytosis. The Rabex-5 GEF activity is autoinhibited by the Rabex-5 CC domain (Rabex-5CC) and activated by the Rabaptin-5 C2-1 domain (Rabaptin-5C21) with yet unknown mechanism. We report here the crystal structures of Rabex-5 in complex with the dimeric Rabaptin-5C21 (Rabaptin-5C212) and in complex with Rabaptin-5C212 and Rab5, along with biophysical and biochemical analyses. We show that Rabex-5CC assumes an amphipathic alpha-helix which binds weakly to the substrate-binding site of the GEF domain, leading to weak autoinhibition of the GEF activity. Binding of Rabaptin-5C21 to Rabex-5 displaces Rabex-5CC to yield a largely exposed substrate-binding site, leading to release of the GEF activity. In the ternary complex the substrate-binding site of Rabex-5 is completely exposed to bind and activate Rab5. Our results reveal the molecular mechanism for the regulation of the Rabex-5 GEF activity.

Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5.,Zhang Z, Zhang T, Wang S, Gong Z, Tang C, Chen J, Ding J Elife (Cambridge). 2014 Jun 23:e02687. doi: 10.7554/eLife.02687. PMID:24957337^[4]

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

References

↑ 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
↑ 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
↑ 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
↑ Zhang Z, Zhang T, Wang S, Gong Z, Tang C, Chen J, Ding J. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5. Elife (Cambridge). 2014 Jun 23:e02687. doi: 10.7554/eLife.02687. PMID:24957337 doi:https://dx.doi.org/10.7554/eLife.02687

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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] Zhang Z, Zhang T, Wang S, Gong Z, Tang C, Chen J, Ding J. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5. Elife (Cambridge). 2014 Jun 23:e02687. doi: 10.7554/eLife.02687. PMID:24957337 doi:https://dx.doi.org/10.7554/eLife.02687

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@@ Line 1: / Line 1: @@
 ==Crystal structure of Rabex-5 CC domain==
-<StructureSection load='4n3x' size='340' side='right' caption='[[4n3x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='4n3x' size='340' side='right'caption='[[4n3x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4n3x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N3X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N3X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4n3x]] 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=4N3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N3X FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n3y|4n3y]], [[4n3z|4n3z]]</td></tr>
+</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=4n3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n3x OCA], [https://pdbe.org/4n3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n3x RCSB], [https://www.ebi.ac.uk/pdbsum/4n3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n3x ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RABEX5 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n3x OCA], [http://pdbe.org/4n3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n3x RCSB], [http://www.ebi.ac.uk/pdbsum/4n3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n3x ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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/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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 17: @@
 </div>
 <div class="pdbe-citations 4n3x" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Rab5 GDP/GTP exchange factor|Rab5 GDP/GTP exchange factor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ding, J]]
+[[Category: Large Structures]]
-[[Category: Zhang, T]]
+[[Category: Ding J]]
-[[Category: Zhang, Z]]
+[[Category: Zhang T]]
-[[Category: Early endosome]]
+[[Category: Zhang Z]]
-[[Category: Endocytosis]]
-[[Category: Gef activity]]
-[[Category: Rab5]]
-[[Category: Rabaptin-5]]
-[[Category: Rabex-5]]

4n3x: Difference between revisions

Revision as of 10:31, 28 December 2022

Crystal structure of Rabex-5 CC domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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