Structural highlights
Function
[DOA1_YEAST] Participates in the regulation of the ubiquitin conjugation pathway involving CDC48 by hindering multiubiquitination of substrates at the CDC48 chaperone. May act by preventing the interaction between CDC48 and the E4 enzyme UFD2, leading to prevent multiubiquitination of substrates and subsequent degradation. Essential for maintaining cellular ubiquitin levels.[1] [2]
Publication Abstract from PubMed
Doa1/Ufd3 is involved in ubiquitin (Ub)-dependent cellular processes in Saccharomyces cerevisiae, and consists of WD40, PFU, and PUL domains. Previous studies showed that the PFU and PUL domains interact with Ub and Hse1, and Cdc48, respectively. However, their detailed functional interactions with Doa1 remained elusive. We report the crystal structure of the PFU-PUL domain pair of yeast Doa1 at 1.9 A resolution. The conserved surface of the PFU domain may be involved in binding to Ub and Hse1. Unexpectedly, the PUL domain consists of an Armadillo (ARM)-like repeat structure. The positively charged concave surface of the PUL domain may bind to the negatively charged C-terminal region of Cdc48. A structural comparison of Doa1 with Ufd2 revealed that they share a similar ARM-like repeat, supporting a model in which Doa1 and Ufd2 compete for Cdc48 binding and may dictate the fate of ubiquitinated proteins in the proteasome pathway.
Crystal Structure of a PFU-PUL Domain Pair of Saccharomyces Cerevisiae Doa1/Ufd3.,Nishimasu R, Komori H, Higuchi Y, Nishimasu H, Hiroaki H Kobe J Med Sci. 2010 Oct 21;56(3):E125-39. PMID:21063153[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Russell NS, Wilkinson KD. Identification of a novel 29-linked polyubiquitin binding protein, Ufd3, using polyubiquitin chain analogues. Biochemistry. 2004 Apr 27;43(16):4844-54. PMID:15096053 doi:10.1021/bi035626r
- ↑ Ghislain M, Dohmen RJ, Levy F, Varshavsky A. Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO J. 1996 Sep 16;15(18):4884-99. PMID:8890162
- ↑ Nishimasu R, Komori H, Higuchi Y, Nishimasu H, Hiroaki H. Crystal Structure of a PFU-PUL Domain Pair of Saccharomyces Cerevisiae Doa1/Ufd3. Kobe J Med Sci. 2010 Oct 21;56(3):E125-39. PMID:21063153
