Structural highlightsFunctionRSP5_YEAST E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Component of a RSP5 ubiquitin ligase complex which specifies polyubiquitination and intracellular trafficking of the general amino acid permease GAP1 as well as other cell surface proteins like GAP1, FUR4, MAL61, PMA1 and STE2. The RSP5-BUL1/2 complex is also necessary for the heat-shock element (HSE)-mediated gene expression, nitrogen starvation GLN3-dependent transcription, pressure-induced differential regulation of the two tryptophan permeases TAT1 and TAT2 and sorting efficiency into multivesicular bodies. Also acts on RBP1. Plays a role in tolerance to o-dinitrobenzene. Involved in actin cytoskeleton organization and dynamics. Ubiquitinates the LAS17-binding proteins LSB1 and PIN3/LSB2 without directing them for degradation and affects LAS17 levels in a SLA1-dependent and LSB1/2-independent manner.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
The Rsp5 ubiquitin ligase contains a non-covalent binding site for ubiquitin within the amino-terminal lobe (N-lobe) of the HECT domain, and the X-ray crystal structure of the HECT-ubiquitin complex has been determined. Hydrophobic patch residues of ubiquitin (L8, I44, V70) were crucial for interaction with Rsp5, and amino-acid alterations at the Rsp5-binding interface resulted in defects in polyubiquitination. Our results support a model in which the N-lobe-binding site acts to localize and orient the distal end of the ubiquitin chain to promote conjugation of the next ubiquitin molecule.
Structure and function of a HECT domain ubiquitin-binding site.,Kim HC, Steffen AM, Oldham ML, Chen J, Huibregtse JM EMBO Rep. 2011 Mar 11. PMID:21399621[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See AlsoReferences
- ↑ Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2563-7. PMID:7708685
- ↑ Yashiroda H, Kaida D, Toh-e A, Kikuchi Y. The PY-motif of Bul1 protein is essential for growth of Saccharomyces cerevisiae under various stress conditions. Gene. 1998 Dec 28;225(1-2):39-46. PMID:9931424
- ↑ Wang G, Yang J, Huibregtse JM. Functional domains of the Rsp5 ubiquitin-protein ligase. Mol Cell Biol. 1999 Jan;19(1):342-52. PMID:9858558
- ↑ Andoh T, Hirata Y, Kikuchi A. PY motifs of Rod1 are required for binding to Rsp5 and for drug resistance. FEBS Lett. 2002 Aug 14;525(1-3):131-4. PMID:12163175
- ↑ Kaida D, Toh-e A, Kikuchi Y. Rsp5-Bul1/2 complex is necessary for the HSE-mediated gene expression in budding yeast. Biochem Biophys Res Commun. 2003 Jul 11;306(4):1037-41. PMID:12821147
- ↑ Abe F, Iida H. Pressure-induced differential regulation of the two tryptophan permeases Tat1 and Tat2 by ubiquitin ligase Rsp5 and its binding proteins, Bul1 and Bul2. Mol Cell Biol. 2003 Nov;23(21):7566-84. PMID:14560004
- ↑ Crespo JL, Helliwell SB, Wiederkehr C, Demougin P, Fowler B, Primig M, Hall MN. NPR1 kinase and RSP5-BUL1/2 ubiquitin ligase control GLN3-dependent transcription in Saccharomyces cerevisiae. J Biol Chem. 2004 Sep 3;279(36):37512-7. Epub 2004 Jul 9. PMID:15247235 doi:10.1074/jbc.M407372200
- ↑ Pizzirusso M, Chang A. Ubiquitin-mediated targeting of a mutant plasma membrane ATPase, Pma1-7, to the endosomal/vacuolar system in yeast. Mol Biol Cell. 2004 May;15(5):2401-9. Epub 2004 Mar 12. PMID:15020711 doi:10.1091/mbc.E03-10-0727
- ↑ Kee Y, Lyon N, Huibregtse JM. The Rsp5 ubiquitin ligase is coupled to and antagonized by the Ubp2 deubiquitinating enzyme. EMBO J. 2005 Jul 6;24(13):2414-24. Epub 2005 Jun 2. PMID:15933713 doi:7600710
- ↑ Feller A, Boeckstaens M, Marini AM, Dubois E. Transduction of the nitrogen signal activating Gln3-mediated transcription is independent of Npr1 kinase and Rsp5-Bul1/2 ubiquitin ligase in Saccharomyces cerevisiae. J Biol Chem. 2006 Sep 29;281(39):28546-54. Epub 2006 Jul 24. PMID:16864574 doi:10.1074/jbc.M605551200
- ↑ Ren J, Kee Y, Huibregtse JM, Piper RC. Hse1, a component of the yeast Hrs-STAM ubiquitin-sorting complex, associates with ubiquitin peptidases and a ligase to control sorting efficiency into multivesicular bodies. Mol Biol Cell. 2007 Jan;18(1):324-35. Epub 2006 Nov 1. PMID:17079730 doi:10.1091/mbc.E06-06-0557
- ↑ Kaminska J, Spiess M, Stawiecka-Mirota M, Monkaityte R, Haguenauer-Tsapis R, Urban-Grimal D, Winsor B, Zoladek T. Yeast Rsp5 ubiquitin ligase affects the actin cytoskeleton in vivo and in vitro. Eur J Cell Biol. 2011 Dec;90(12):1016-28. doi: 10.1016/j.ejcb.2011.08.002. Epub, 2011 Oct 14. PMID:22000681 doi:10.1016/j.ejcb.2011.08.002
- ↑ Kim HC, Steffen AM, Oldham ML, Chen J, Huibregtse JM. Structure and function of a HECT domain ubiquitin-binding site. EMBO Rep. 2011 Mar 11. PMID:21399621 doi:10.1038/embor.2011.23
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