Proteopedia

2mr9

NMR structure of UBA domain of DNA-damage-inducible 1 protein (Ddi1)NMR structure of UBA domain of DNA-damage-inducible 1 protein (Ddi1)

Structural highlights

2mr9 is a 1 chain structure with sequence from Saccharomyces cerevisiae S288C. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
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