Crystal Structure of a PFU-PUL Domain Pair of Saccharomyces Cerevisiae Doa1/ufd3

摘要

Doa1/Ufd3 is involved in ubiquitin (Ub)-dependent cellular processes inSaccharomyces cerevisiae, and consists of WD40, PFU, and PUL domains. Previousstudies showed that the PFU and PUL domains interact with Ub and Hse1, and Cdc48,respectively. However, their detailed functional interactions with Doa1 remainedelusive. We report the crystal structure of the PFU-PUL domain pair of yeast Doa1 at1.9 ? resolution. The conserved surface of the PFU domain may be involved in bindingto Ub and Hse1. Unexpectedly, the PUL domain consists of an Armadillo (ARM)-likerepeat structure. The positively charged concave surface of the PUL domain may bindto the negatively charged C-terminal region of Cdc48. A structural comparison of Doa1with Ufd2 revealed that they share a similar ARM-like repeat, supporting a model inwhich Doa1 and Ufd2 compete for Cdc48 binding and may dictate the fate ofubiquitinated proteins in the proteasome pathway.