|
|
| (5 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==NMR structure of UBA domain of DNA-damage-inducible 1 protein (Ddi1)== | | ==NMR structure of UBA domain of DNA-damage-inducible 1 protein (Ddi1)== |
| - | <StructureSection load='2mr9' size='340' side='right' caption='[[2mr9]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2mr9' size='340' side='right'caption='[[2mr9]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mr9]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MR9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MR9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mr9]] 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=2MR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MR9 FirstGlance]. <br> |
| - | </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=2mr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mr9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mr9 RCSB], [http://www.ebi.ac.uk/pdbsum/2mr9 PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mr9 OCA], [https://pdbe.org/2mr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mr9 RCSB], [https://www.ebi.ac.uk/pdbsum/2mr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mr9 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 == |
| | + | Ddi1 belongs to a family of shuttle proteins targeting polyubiquitinated substrates for proteasomal degradation. Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized. We determined the structure and binding properties of the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of Ddi1 from Saccharomyces cerevisiae. We found that while Ddi1UBA forms a characteristic UBA:ubiquitin complex, Ddi1UBL has entirely uncharacteristic binding preferences. Despite having a ubiquitin-like fold, Ddi1UBL does not interact with typical UBL receptors but unexpectedly binds ubiquitin, forming a unique interface mediated by hydrophobic contacts and by salt bridges between oppositely charged residues of Ddi1UBL and ubiquitin. In stark contrast to ubiquitin and other UBLs, the beta-sheet surface of Ddi1UBL is negatively charged and therefore is recognized in a completely different way. The dual functionality of Ddi1UBL, capable of binding both ubiquitin and proteasome, suggests an intriguing mechanism for Ddi1 as a proteasomal shuttle. |
| | + | |
| | + | DNA-Damage-Inducible 1 Protein (Ddi1) Contains an Uncharacteristic Ubiquitin-like Domain that Binds Ubiquitin.,Nowicka U, Zhang D, Walker O, Krutauz D, Castaneda CA, Chaturvedi A, Chen TY, Reis N, Glickman MH, Fushman D Structure. 2015 Mar 3;23(3):542-57. doi: 10.1016/j.str.2015.01.010. Epub 2015 Feb, 19. PMID:25703377<ref>PMID:25703377</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2mr9" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fushman, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, D]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Ddi1]] | + | [[Category: Fushman D]] |
| - | [[Category: Dna-damage-inducible 1 protein]] | + | [[Category: Zhang D]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Uba]]
| + | |
| - | [[Category: Ubiquitin associated domain]]
| + | |
| 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
Ddi1 belongs to a family of shuttle proteins targeting polyubiquitinated substrates for proteasomal degradation. Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized. We determined the structure and binding properties of the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of Ddi1 from Saccharomyces cerevisiae. We found that while Ddi1UBA forms a characteristic UBA:ubiquitin complex, Ddi1UBL has entirely uncharacteristic binding preferences. Despite having a ubiquitin-like fold, Ddi1UBL does not interact with typical UBL receptors but unexpectedly binds ubiquitin, forming a unique interface mediated by hydrophobic contacts and by salt bridges between oppositely charged residues of Ddi1UBL and ubiquitin. In stark contrast to ubiquitin and other UBLs, the beta-sheet surface of Ddi1UBL is negatively charged and therefore is recognized in a completely different way. The dual functionality of Ddi1UBL, capable of binding both ubiquitin and proteasome, suggests an intriguing mechanism for Ddi1 as a proteasomal shuttle.
DNA-Damage-Inducible 1 Protein (Ddi1) Contains an Uncharacteristic Ubiquitin-like Domain that Binds Ubiquitin.,Nowicka U, Zhang D, Walker O, Krutauz D, Castaneda CA, Chaturvedi A, Chen TY, Reis N, Glickman MH, Fushman D Structure. 2015 Mar 3;23(3):542-57. doi: 10.1016/j.str.2015.01.010. Epub 2015 Feb, 19. PMID:25703377[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
- ↑ Nowicka U, Zhang D, Walker O, Krutauz D, Castaneda CA, Chaturvedi A, Chen TY, Reis N, Glickman MH, Fushman D. DNA-Damage-Inducible 1 Protein (Ddi1) Contains an Uncharacteristic Ubiquitin-like Domain that Binds Ubiquitin. Structure. 2015 Mar 3;23(3):542-57. doi: 10.1016/j.str.2015.01.010. Epub 2015 Feb, 19. PMID:25703377 doi:http://dx.doi.org/10.1016/j.str.2015.01.010
|
