title: UAS domain of Ubxd8 and FAF1 polymerizes upon interaction with long-chain unsaturated fatty acids.
abstract: Ubxd8, a multidomain protein sensor for long-chain 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.
authors.affiliation: Departments of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Hyeonwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Biophysics University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Departments of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: David
authors.initials: D
authors.lastname: Meng
authors.affiliation: Departments of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Russell
authors.affiliation: Departments of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Joon No
authors.initials: JN
authors.lastname: Lee
authors.affiliation: Departments of Molecular Genetics University of Texas Southwestern Medical Center, Dallas, TX 75390. Electronic address: jin.ye@utsouthwestern.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D003412:Cricetulus; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D058105:Polymerization; D017434:Protein Structure, Tertiary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001798:Blood Proteins; C490780:FAF1 protein, human; C468782:FAF2 protein, human; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins
keywords: Fas-associated factor 1; Insig-1; protein degradation