Molecular recognition of nitrated fatty acids by PPARγ

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Abstract
PPARγ is a nuclear receptor that regulates metabolic homeostasis. It is activated by nitrated and oxidized fatty acids. The crystal structure of the ligand binding domain of PPARγ in complex with a physiological ligand, nitrated linoleic acid, is now described, showing differences with synthetic agonists that may have physiological relevance. Peroxisome proliferator activated receptor-γ (PPARγ) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPARγ ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPARγ. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPARγ discrimination of various naturally occurring fatty acid derivatives.