Nishimasu Rieko, Komori Hirofumi, Higuchi Yoshiki, Nishimasu Hiroshi, Hiroaki Hidekazu
Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Kobe J Med Sci. 2010 Oct 21;56(3):E125-39.
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.
Doa1/Ufd3参与酿酒酵母中依赖泛素（Ub）的细胞过程，由WD40、PFU和PUL结构域组成。先前的研究表明，PFU和PUL结构域分别与Ub和Hse1以及Cdc48相互作用。然而，它们与Doa1的详细功能相互作用仍不清楚。我们报道了酵母Doa1的PFU-PUL结构域对的晶体结构，分辨率为1.9 Å。PFU结构域的保守表面可能参与与Ub和Hse1的结合。出乎意料的是，PUL结构域由类似犰狳（ARM）的重复结构组成。PUL结构域带正电荷的凹面可能与Cdc48带负电荷的C末端区域结合。Doa1与Ufd2的结构比较表明，它们共享类似的ARM样重复结构，支持一种模型，即Doa1和Ufd2竞争与Cdc48结合，并可能决定蛋白酶体途径中泛素化蛋白的命运。
