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| - | ==UBL domain of the yeast DNA damage-inducible protein homolog 1== | + | ==Solution structure of the UBL domain of yeast Ddi1== |
| - | <StructureSection load='2n7e' size='340' side='right' caption='[[2n7e]], [[NMR_Ensembles_of_Models | 43 NMR models]]' scene=''> | + | <StructureSection load='2n7e' size='340' side='right'caption='[[2n7e]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n7e]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N7E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N7E FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n7d|2n7d]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n7e OCA], [https://pdbe.org/2n7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n7e RCSB], [https://www.ebi.ac.uk/pdbsum/2n7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n7e ProSAT]</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=2n7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n7e OCA], [http://pdbe.org/2n7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n7e RCSB], [http://www.ebi.ac.uk/pdbsum/2n7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n7e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DDI1_YEAST DDI1_YEAST]] Acts as a linker between the 19S proteasome and polyubiquitinated proteins like the HO endonuclease and UFO1 via UBA domain interactions with ubiquitin for their subsequent degradation. Required for S-phase checkpoint control. Appears to act as negative regulator of constitutive exocytosis. May act at the level of secretory vesicle docking and fusion as a competitive inhibitor of SNARE assembly.<ref>PMID:10330187</ref> <ref>PMID:11238935</ref> <ref>PMID:12051757</ref> <ref>PMID:12925750</ref> <ref>PMID:15964793</ref> <ref>PMID:17144915</ref> <ref>PMID:16478980</ref> | + | [https://www.uniprot.org/uniprot/DDI1_YEAST DDI1_YEAST] Acts as a linker between the 19S proteasome and polyubiquitinated proteins like the HO endonuclease and UFO1 via UBA domain interactions with ubiquitin for their subsequent degradation. Required for S-phase checkpoint control. Appears to act as negative regulator of constitutive exocytosis. May act at the level of secretory vesicle docking and fusion as a competitive inhibitor of SNARE assembly.<ref>PMID:10330187</ref> <ref>PMID:11238935</ref> <ref>PMID:12051757</ref> <ref>PMID:12925750</ref> <ref>PMID:15964793</ref> <ref>PMID:17144915</ref> <ref>PMID:16478980</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains. |
| | + | |
| | + | Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family.,Trempe JF, Saskova KG, Siva M, Ratcliffe CD, Veverka V, Hoegl A, Menade M, Feng X, Shenker S, Svoboda M, Kozisek M, Konvalinka J, Gehring K Sci Rep. 2016 Sep 20;6:33671. doi: 10.1038/srep33671. PMID:27646017<ref>PMID:27646017</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2n7e" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Saskova, K Grantz]] | + | [[Category: Large Structures]] |
| - | [[Category: Siva, M]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Veverka, V]] | + | [[Category: Grantz Saskova K]] |
| - | [[Category: Ddi1]] | + | [[Category: Siva M]] |
| - | [[Category: Unknown function]] | + | [[Category: Veverka V]] |
| Structural highlights
Function
DDI1_YEAST Acts as a linker between the 19S proteasome and polyubiquitinated proteins like the HO endonuclease and UFO1 via UBA domain interactions with ubiquitin for their subsequent degradation. Required for S-phase checkpoint control. Appears to act as negative regulator of constitutive exocytosis. May act at the level of secretory vesicle docking and fusion as a competitive inhibitor of SNARE assembly.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.
Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family.,Trempe JF, Saskova KG, Siva M, Ratcliffe CD, Veverka V, Hoegl A, Menade M, Feng X, Shenker S, Svoboda M, Kozisek M, Konvalinka J, Gehring K Sci Rep. 2016 Sep 20;6:33671. doi: 10.1038/srep33671. PMID:27646017[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lustgarten V, Gerst JE. Yeast VSM1 encodes a v-SNARE binding protein that may act as a negative regulator of constitutive exocytosis. Mol Cell Biol. 1999 Jun;19(6):4480-94. PMID:10330187
- ↑ Clarke DJ, Mondesert G, Segal M, Bertolaet BL, Jensen S, Wolff M, Henze M, Reed SI. Dosage suppressors of pds1 implicate ubiquitin-associated domains in checkpoint control. Mol Cell Biol. 2001 Mar;21(6):1997-2007. PMID:11238935 doi:http://dx.doi.org/10.1128/MCB.21.6.1997-2007.2001
- ↑ Saeki Y, Saitoh A, Toh-e A, Yokosawa H. Ubiquitin-like proteins and Rpn10 play cooperative roles in ubiquitin-dependent proteolysis. Biochem Biophys Res Commun. 2002 May 10;293(3):986-92. PMID:12051757 doi:http://dx.doi.org/10.1016/S0006-291X(02)00340-6
- ↑ Marash M, Gerst JE. Phosphorylation of the autoinhibitory domain of the Sso t-SNAREs promotes binding of the Vsm1 SNARE regulator in yeast. Mol Biol Cell. 2003 Aug;14(8):3114-25. Epub 2003 May 3. PMID:12925750 doi:http://dx.doi.org/10.1091/mbc.E02-12-0804
- ↑ Kaplun L, Tzirkin R, Bakhrat A, Shabek N, Ivantsiv Y, Raveh D. The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated degradation of Ho endonuclease. Mol Cell Biol. 2005 Jul;25(13):5355-62. PMID:15964793 doi:http://dx.doi.org/25/13/5355
- ↑ Diaz-Martinez LA, Kang Y, Walters KJ, Clarke DJ. Yeast UBL-UBA proteins have partially redundant functions in cell cycle control. Cell Div. 2006 Dec 4;1:28. PMID:17144915 doi:http://dx.doi.org/1747-1028-1-28
- ↑ Ivantsiv Y, Kaplun L, Tzirkin-Goldin R, Shabek N, Raveh D. Unique role for the UbL-UbA protein Ddi1 in turnover of SCFUfo1 complexes. Mol Cell Biol. 2006 Mar;26(5):1579-88. PMID:16478980 doi:http://dx.doi.org/26/5/1579
- ↑ Trempe JF, Saskova KG, Siva M, Ratcliffe CD, Veverka V, Hoegl A, Menade M, Feng X, Shenker S, Svoboda M, Kozisek M, Konvalinka J, Gehring K. Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family. Sci Rep. 2016 Sep 20;6:33671. doi: 10.1038/srep33671. PMID:27646017 doi:http://dx.doi.org/10.1038/srep33671
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