The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97

International Graduate School of Arts and Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
FEBS Journal (Impact Factor: 4). 12/2006; 273(21):4959-71. DOI: 10.1111/j.1742-4658.2006.05494.x
Source: PubMed


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 beta-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 valosine-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.

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    • "While the N-terminal domains (NTD) of Pex1p are positioned on top of the rings, the N-terminal domains (NTD) of Pex6p fold back and are situated aside of the double ring, forming the vertices of an atypically triangular geometry when the complex is viewed from top. By interactions of the Pex6p NTD to Pex15p [77], the Pex1p–Pex6p-complex is possibly anchored at its vertices to the peroxisomal membrane, whereby the affinity of the Pex1p NTD to phospholipids might support the attachment to the membrane [155]. Interestingly, D1 and D2 domains of the subunits are tilted, allowing the NTD of Pex6p to contact the D2 domain of the adjacent Pex1p subunit [76] [87]. "
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