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The common phospholipid‐binding activity of the N‐terminal domains of PEX1 and VCP/p97
Author(s) -
Shiozawa Kumiko,
Goda Natsuko,
Shimizu Toshiyuki,
Mizuguchi Kenji,
Kondo Naomi,
Shimozawa Nobuyuki,
Shirakawa Masahiro,
Hiroaki Hidekazu
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05494.x
Subject(s) - aaa proteins , biology , biochemistry , signal transducing adaptor protein , protein domain , atpase , microbiology and biotechnology , signal transduction , enzyme , gene
PEX1 is a type II AAA‐ATPase that is indispensable for biogenesis and maintenance of the peroxisome, an organelle responsible for the primary metabolism of lipids, such as β‐oxidation and lipid biosynthesis. Recently, we demonstrated a striking structural similarity between its N‐terminal domain and those of other membrane‐related AAA‐ATPases, such as valosin‐containing protein (p97). The N‐terminal domain of valosine‐containing protein serves as an interface to its adaptor proteins p47 and Ufd1, whereas the physiologic interaction partner of the N‐terminal domain of PEX1 remains unknown. Here we found that N‐terminal domains isolated from valosine‐containing protein, as well as from PEX1, bind phosphoinositides. The N‐terminal domain of PEX1 appears to preferentially bind phosphatidylinositol 3‐monophosphate and phosphatidylinositol 4‐monophosphate, whereas the N‐terminal domain of valosine‐containing protein displays broad and nonspecific lipid binding. Although N ‐ethylmaleimide‐sensitive fusion protein, CDC48 and Ufd1 have structures similar to that of valosine‐containing protein, they displayed lipid specificity similar to that of the N‐terminal domain of PEX1 in the assays. By mutational analysis, we demonstrate that a conserved arginine surrounded by hydrophobic residues is essential for lipid binding, despite very low sequence similarity between PEX1 and valosine‐containing protein.