Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3.
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 Å 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.
Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Rieko
R
Nishimasu
Hirofumi
H
Komori
Yoshiki
Y
Higuchi
Hiroshi
H
Nishimasu
Hidekazu
H
Hiroaki
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D051186:Armadillo Domain Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D008840:Microfilament Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; C099944:DOA1 protein, S cerevisiae; D008840:Microfilament Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C055324:phospholipase A2-activating protein; D046988:Proteasome Endopeptidase Complex