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Molecular recognition of nitrated fatty acids by PPARγ

Abstract

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.

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Figure 1: The structure of the PPARγ LBD and LNO2 complex.
Figure 2: The structural determinants of the PPARγ LBD and LNO2 complex.
Figure 3: Functional correlation of the LNO2–PPARγ interactions.

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Acknowledgements

We thank W.D. Tolbert and Z. Wawrzak for assistance in data collection at the DND-CAT of the Advanced Photon Source. Use of the Advanced Photon Source was supported by the US Office of Science of the US Department of Energy. This work was supported in part by the Jay and Betty Van Andel Foundation (H.E.X.), US National Institutes of Health Grants DK071662 and DK066202 (H.E.X.), HL089301 (H.E.X. and Y.L.), HL68878, HL089544 and HL75397 (Y.E.C.), HL58115 and HL64937 (B.A.F.), American Diabetes Association (P.R.S.B.) and awards from the American Heart Association (Y.L., F.J.S.).

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Correspondence to Yong Li or H Eric Xu.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 348 kb)

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Li, Y., Zhang, J., Schopfer, F. et al. Molecular recognition of nitrated fatty acids by PPARγ. Nat Struct Mol Biol 15, 865–867 (2008). https://doi.org/10.1038/nsmb.1447

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