2MRO

Structure of the complex of ubiquitin and the UBA domain from DNA-damage-inducible 1 protein (Ddi1)

Summary for 2MRO

• Entry DOI: 10.2210/pdb2mro/pdb
• Related: 1d3z 2MR9
• Descriptor: Polyubiquitin-B, DNA damage-inducible protein 1 (2 entities in total)
• Functional Keywords: dna-damage-inducible 1 protein, ubiquitin associated domain, ddi1, uba, hydrolase-signaling protein complex, transport protein-signaling protein complex, transport protein/signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 13322.20

Authors

Zhang, D.,Fushman, D. (deposition date: 2014-07-14, release date: 2015-02-04, Last modification date: 2024-05-22)

Primary citation

Nowicka, U.,Zhang, D.,Walker, O.,Krutauz, D.,Castaneda, C.A.,Chaturvedi, A.,Chen, T.Y.,Reis, N.,Glickman, M.H.,Fushman, D.
DNA-Damage-Inducible 1 Protein (Ddi1) Contains an Uncharacteristic Ubiquitin-like Domain that Binds Ubiquitin.
Structure, 23:542-557, 2015

PubMed 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.

PubMed: 25703377
DOI: 10.1016/j.str.2015.01.010

Experimental method

SOLUTION NMR