Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3

Rieko Nishimasu; Hirofumi Komori; Yoshiki Higuchi; Hiroshi Nishimasu; Hidekazu Hiroaki

Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3

Kobe J Med Sci. 2010 Oct 21;56(3):E125-39.

Authors

Rieko Nishimasu¹, Hirofumi Komori, Yoshiki Higuchi, Hiroshi Nishimasu, Hidekazu Hiroaki

Affiliation

¹ Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.

PMID: 21063153

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry*
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Amino Acid Sequence
Armadillo Domain Proteins / chemistry
Crystallography, X-Ray*
Microfilament Proteins / chemistry
Molecular Sequence Data
Proteasome Endopeptidase Complex / chemistry
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
Protein Binding / physiology
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins / chemistry
Saccharomyces cerevisiae / chemistry*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Ubiquitination / physiology

Substances

Adaptor Proteins, Signal Transducing
Armadillo Domain Proteins
DOA1 protein, S cerevisiae
Microfilament Proteins
Proteins
Saccharomyces cerevisiae Proteins
phospholipase A2-activating protein
Proteasome Endopeptidase Complex