DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin

Urszula Nowicka, Daoning Zhang, Olivier Walker, Daria Krutauz, Carlos A. Castañeda, Apurva Chaturvedi, Tony Y. Chen, Noa Reis, Michael H. Glickman, David Fushman

Research output: Research - peer-reviewArticle

  • 14 Citations

Abstract

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 β-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.

LanguageEnglish (US)
Pages542-557
Number of pages16
JournalStructure
Volume23
Issue number3
DOIs
StatePublished - Mar 3 2015
Externally publishedYes

Fingerprint

Ubiquitin
DNA Damage
Proteins
Saccharomyces cerevisiae Proteins
Protein Transport
Proteasome Endopeptidase Complex
Salts
beta-Strand Protein Conformation

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Nowicka, U., Zhang, D., Walker, O., Krutauz, D., Castañeda, C. A., Chaturvedi, A., ... Fushman, D. (2015). DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin. Structure, 23(3), 542-557. DOI: 10.1016/j.str.2015.01.010

DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin. / Nowicka, Urszula; Zhang, Daoning; Walker, Olivier; Krutauz, Daria; Castañeda, Carlos A.; Chaturvedi, Apurva; Chen, Tony Y.; Reis, Noa; Glickman, Michael H.; Fushman, David.

In: Structure, Vol. 23, No. 3, 03.03.2015, p. 542-557.

Research output: Research - peer-reviewArticle

Nowicka, U, Zhang, D, Walker, O, Krutauz, D, Castañeda, CA, Chaturvedi, A, Chen, TY, Reis, N, Glickman, MH & Fushman, D 2015, 'DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin' Structure, vol 23, no. 3, pp. 542-557. DOI: 10.1016/j.str.2015.01.010
Nowicka U, Zhang D, Walker O, Krutauz D, Castañeda CA, Chaturvedi A et al. DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin. Structure. 2015 Mar 3;23(3):542-557. Available from, DOI: 10.1016/j.str.2015.01.010
Nowicka, Urszula ; Zhang, Daoning ; Walker, Olivier ; Krutauz, Daria ; Castañeda, Carlos A. ; Chaturvedi, Apurva ; Chen, Tony Y. ; Reis, Noa ; Glickman, Michael H. ; Fushman, David. / DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin. In: Structure. 2015 ; Vol. 23, No. 3. pp. 542-557
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