Abstract
Ubxd8, a multidomain protein sensor for longchain unsaturated fatty acids (FAs), plays a crucial role to maintain cellular homeostasis of FAs. Ubxd8 polymerizes upon interaction with long-chain unsaturated FAs, but the molecular mechanism involved in this polymerization remains unclear. Here we report that the UAS domain of Ubxd8 mediates this polymerization. We show that a positively charged surface area in the domain is required for the reaction. Mutations changing the positively charged residues in this area to glutamates prevented long-chain unsaturated FAs from inducing oligomerization of Ubxd8. Consequently, the mutant protein no longer responded to regulation by long-chain unsaturated FAs in cultured cells. Long-chain unsaturated FAs also induced polymerization of Fas-associated factor 1 (FAF1), the only other mammalian protein that contains a UAS domain homologous to that of Ubxd8. These results provide further insights into protein- FA interactions by identifying the UAS domain as a motif interacting with long-chain unsaturated FAs.
Original language | English (US) |
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Pages (from-to) | 2144-2152 |
Number of pages | 9 |
Journal | Journal of lipid research |
Volume | 54 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2013 |
Keywords
- Fas-associated factor 1
- Insig-1
- Protein degradation
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology