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4q9u

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Revision as of 21:24, 24 December 2014

Crystal structure of the Rab5, Rabex-5delta and Rabaptin-5C21 complex

Structural highlights

4q9u is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4n3x, 4n3y, 4n3z
Resources:	FirstGlance, OCA, RCSB, PDBsum

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] [RABE1_HUMAN] Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A.^[4] ^[5] ^[6] ^[7] [RAB5A_HUMAN] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.^[8]

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^[9]

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
↑ Stenmark H, Vitale G, Ullrich O, Zerial M. Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion. Cell. 1995 Nov 3;83(3):423-32. PMID:8521472
↑ Nagelkerken B, Van Anken E, Van Raak M, Gerez L, Mohrmann K, Van Uden N, Holthuizen J, Pelkmans L, Van Der Sluijs P. Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles. Biochem J. 2000 Mar 15;346 Pt 3:593-601. PMID:10698684
↑ 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
↑ Deneka M, Neeft M, Popa I, van Oort M, Sprong H, Oorschot V, Klumperman J, Schu P, van der Sluijs P. Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes. EMBO J. 2003 Jun 2;22(11):2645-57. PMID:12773381 doi:http://dx.doi.org/10.1093/emboj/cdg257
↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
↑ 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:http://dx.doi.org/10.7554/eLife.02687

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q9u"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4q9u]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q9U FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n3x|4n3x]], [[4n3y|4n3y]], [[4n3z|4n3z]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n3x|4n3x]], [[4n3y|4n3y]], [[4n3z|4n3z]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4q9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9u RCSB], [http://www.ebi.ac.uk/pdbsum/4q9u PDBsum]</span></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=4q9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q9u RCSB], [http://www.ebi.ac.uk/pdbsum/4q9u PDBsum]</span></td></tr>
-<table>
+</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>  [[http://www.uniprot.org/uniprot/RABE1_HUMAN RABE1_HUMAN]] Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A.<ref>PMID:8521472</ref> <ref>PMID:10698684</ref> <ref>PMID:11452015</ref> <ref>PMID:12773381</ref>  [[http://www.uniprot.org/uniprot/RAB5A_HUMAN RAB5A_HUMAN]] Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension.<ref>PMID:14978216</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 20: @@
 __TOC__
 </StructureSection>
-[[Category: Ding, J.]]
+[[Category: Ding, J]]
-[[Category: Zhang, T.]]
+[[Category: Zhang, T]]
-[[Category: Zhang, Z.]]
+[[Category: Zhang, Z]]
 [[Category: Coiled-coil]]
 [[Category: Early endosome]]

4q9u

From Proteopedia

Revision as of 21:24, 24 December 2014

Crystal structure of the Rab5, Rabex-5delta and Rabaptin-5C21 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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