The Rab5 guanine nucleotide exchange factor Rabex-5 binds ubiquitin (Ub) and functions as a Ub ligase through an atypical Ub-interacting motif and a zinc finger domain - PubMed (original) (raw)
. 2006 Mar 10;281(10):6874-83.
doi: 10.1074/jbc.M509939200. Epub 2006 Jan 5.
Affiliations
- PMID: 16407276
- DOI: 10.1074/jbc.M509939200
Free article
The Rab5 guanine nucleotide exchange factor Rabex-5 binds ubiquitin (Ub) and functions as a Ub ligase through an atypical Ub-interacting motif and a zinc finger domain
Rafael Mattera et al. J Biol Chem. 2006.
Free article
Abstract
Rabex-5, the mammalian orthologue of yeast Vps9p, is a guanine nucleotide exchange factor for Rab5. Rabex-5 forms a tight complex with Rabaptin-5, a multivalent adaptor protein that also binds to Rab4, Rab5, and to domains present in gamma-adaptins and the Golgi-localized, gamma-ear-containing, ARF-binding proteins (GGAs). Rabaptin-5 augments the Rabex-5 exchange activity, thus generating GTP-bound, membrane-associated Rab5 that, in turn, binds Rabaptin-5 and stabilizes the Rabex-5.Rabaptin-5 complex on endosomes. Although the Rabex-5.Rabaptin-5 complex is critical to the regulation of endosomal fusion, the structural determinants of this interaction are unknown. Likewise, the possible binding and covalent attachment of ubiquitin to Rabex-5, two modifications that are critical to the function of yeast Vps9p in endosomal transport, have not been studied. In this study, we identify the 401-462 and 551-661 coiled-coils as the regions in Rabex-5 and Rabaptin-5, respectively, that interact with one another. We also demonstrate that Rabex-5 undergoes ubiquitination and binds ubiquitin, though not via its proposed C-terminal CUE-like domain. Instead, the N-terminal region of Rabex-5 (residues 1-76), comprising an A20-like Cys2/Cys2 zinc finger and an adjacent alpha-helix, is important for ubiquitin binding and ubiquitination. Importantly, we demonstrate that the Rabex-5 zinc finger displays ubiquitin ligase (E3) activity. These observations extend our understanding of the regulation of Rabex-5 by Rabaptin-5. Moreover, the demonstration that Rabex-5 is a ubiquitin ligase that binds ubiquitin and undergoes ubiquitination indicates that its role in endosome fusion may be subject to additional regulation by ubiquitin-dependent modifications.
Similar articles
- Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5.
Lee S, Tsai YC, Mattera R, Smith WJ, Kostelansky MS, Weissman AM, Bonifacino JS, Hurley JH. Lee S, et al. Nat Struct Mol Biol. 2006 Mar;13(3):264-71. doi: 10.1038/nsmb1064. Epub 2006 Feb 5. Nat Struct Mol Biol. 2006. PMID: 16462746 Free PMC article. - Rabaptin-5-independent membrane targeting and Rab5 activation by Rabex-5 in the cell.
Zhu H, Zhu G, Liu J, Liang Z, Zhang XC, Li G. Zhu H, et al. Mol Biol Cell. 2007 Oct;18(10):4119-28. doi: 10.1091/mbc.e07-02-0100. Epub 2007 Aug 15. Mol Biol Cell. 2007. PMID: 17699593 Free PMC article. - 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. Penengo L, et al. Cell. 2006 Mar 24;124(6):1183-95. doi: 10.1016/j.cell.2006.02.020. Epub 2006 Feb 23. Cell. 2006. PMID: 16499958 - A new side to ubiquitin.
Raiborg C, Slagsvold T, Stenmark H. Raiborg C, et al. Trends Biochem Sci. 2006 Oct;31(10):541-4. doi: 10.1016/j.tibs.2006.07.009. Epub 2006 Aug 9. Trends Biochem Sci. 2006. PMID: 16901703 Review. - [Effectors of GTPase Rab5 in endocytosis and signal transduction].
Olchowik M, Miaczyńska M. Olchowik M, et al. Postepy Biochem. 2009;55(2):171-80. Postepy Biochem. 2009. PMID: 19824473 Review. Polish.
Cited by
- Ubiquitin-binding domains.
Hurley JH, Lee S, Prag G. Hurley JH, et al. Biochem J. 2006 Nov 1;399(3):361-72. doi: 10.1042/BJ20061138. Biochem J. 2006. PMID: 17034365 Free PMC article. Review. - Functional determinants of ras interference 1 mutants required for their inhbitory activity on endocytosis.
Galvis A, Giambini H, Villasana Z, Barbieri MA. Galvis A, et al. Exp Cell Res. 2009 Mar 10;315(5):820-35. doi: 10.1016/j.yexcr.2008.12.003. Epub 2008 Dec 16. Exp Cell Res. 2009. PMID: 19118546 Free PMC article. - A non-linear system patterns Rab5 GTPase on the membrane.
Cezanne A, Lauer J, Solomatina A, Sbalzarini IF, Zerial M. Cezanne A, et al. Elife. 2020 Jun 8;9:e54434. doi: 10.7554/eLife.54434. Elife. 2020. PMID: 32510320 Free PMC article. - Synthetic biology approach to reconstituting the ubiquitylation cascade in bacteria.
Keren-Kaplan T, Attali I, Motamedchaboki K, Davis BA, Tanner N, Reshef Y, Laudon E, Kolot M, Levin-Kravets O, Kleifeld O, Glickman M, Horazdovsky BF, Wolf DA, Prag G. Keren-Kaplan T, et al. EMBO J. 2012 Jan 18;31(2):378-90. doi: 10.1038/emboj.2011.397. Epub 2011 Nov 11. EMBO J. 2012. PMID: 22081111 Free PMC article. - Loss of endocytosis-associated RabGEF1 causes aberrant morphogenesis and altered autophagy in photoreceptors leading to retinal degeneration.
Hargrove-Grimes P, Mondal AK, Gumerson J, Nellissery J, Aponte AM, Gieser L, Qian H, Fariss RN, Bonifacino JS, Li T, Swaroop A. Hargrove-Grimes P, et al. PLoS Genet. 2020 Dec 23;16(12):e1009259. doi: 10.1371/journal.pgen.1009259. eCollection 2020 Dec. PLoS Genet. 2020. PMID: 33362196 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials