2ot3 | pdb_00002ot3

Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21

Structural highlights

2ot3 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1txu, 1z0i
Gene:	RABGEF1, RABEX5 (HUMAN), RAB21, KIAA0118 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, 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] [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 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.

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.

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
↑ Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, Fassler R, Kallio M, Ivaska J. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell. 2008 Sep;15(3):371-85. PMID:18804435 doi:https://dx.doi.org/S1534-5807(08)00324-9
↑ Delprato A, Lambright DG. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:17450153 doi:10.1038/nsmb1232

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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] Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, Fassler R, Kallio M, Ivaska J. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell. 2008 Sep;15(3):371-85. PMID:18804435 doi:https://dx.doi.org/S1534-5807(08)00324-9

[5] Delprato A, Lambright DG. Structural basis for Rab GTPase activation by VPS9 domain exchange factors. Nat Struct Mol Biol. 2007 May;14(5):406-12. Epub 2007 Apr 22. PMID:17450153 doi:10.1038/nsmb1232

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2ot3 | pdb_00002ot3

Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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