4lcd

From Proteopedia

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Revision as of 17:07, 24 December 2014

Structure of an Rsp5xUbxSna3 complex: Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3

Structural highlights

4lcd is a 6 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae s288c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MDP1, NPI1, RSP5, SYGP-ORF41, YER125W (Saccharomyces cerevisiae S288c), UBC, UBIQUITIN (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[RSP5_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] [UBC_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.^[13] ^[14]

Publication Abstract from PubMed

Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2 approximately ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT approximately ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3 approximately ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3 approximately ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation. DOI:http://dx.doi.org/10.7554/eLife.00828.001.

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3.,Kamadurai HB, Qiu Y, Deng A, Harrison JS, Macdonald C, Actis M, Rodrigues P, Miller DJ, Souphron J, Lewis SM, Kurinov I, Fujii N, Hammel M, Piper R, Kuhlman B, Schulman BA Elife. 2013 Aug 8;2:e00828. doi: 10.7554/eLife.00828. Print 2013. PMID:23936628^[15]

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

References

↑ 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
↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
↑ Kamadurai HB, Qiu Y, Deng A, Harrison JS, Macdonald C, Actis M, Rodrigues P, Miller DJ, Souphron J, Lewis SM, Kurinov I, Fujii N, Hammel M, Piper R, Kuhlman B, Schulman BA. Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3. Elife. 2013 Aug 8;2:e00828. doi: 10.7554/eLife.00828. Print 2013. PMID:23936628 doi:10.7554/eLife.00828

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 6: / Line 6: @@
 <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=4lcd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lcd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lcd RCSB], [http://www.ebi.ac.uk/pdbsum/4lcd PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/RSP5_YEAST RSP5_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.<ref>PMID:7708685</ref> <ref>PMID:9931424</ref> <ref>PMID:9858558</ref> <ref>PMID:12163175</ref> <ref>PMID:12821147</ref> <ref>PMID:14560004</ref> <ref>PMID:15247235</ref> <ref>PMID:15020711</ref> <ref>PMID:15933713</ref> <ref>PMID:16864574</ref> <ref>PMID:17079730</ref> <ref>PMID:22000681</ref>  [[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4lcd

From Proteopedia

Revision as of 17:07, 24 December 2014

Structure of an Rsp5xUbxSna3 complex: Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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