The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Structural basis for the activation of PPARγ by oxidized fatty acids
Open accessAbstract
The nuclear receptor peroxisome proliferator–activated receptor-γ (PPARγ) has important roles in adipogenesis and immune response as well as roles in both lipid and carbohydrate metabolism. Although synthetic agonists for PPARγ are widely used as insulin sensitizers, the identity of the natural ligand(s) for PPARγ is still not clear. Suggested natural ligands include 15-deoxy-Δ12,14-prostaglandin J2 and oxidized fatty acids such as 9-HODE and 13-HODE. Crystal structures of PPARγ have revealed the mode of recognition for synthetic compounds. Here we report structures of PPARγ bound to oxidized fatty acids that are likely to be natural ligands for this receptor. These structures reveal that the receptor can (i) simultaneously bind two fatty acids and (ii) couple covalently with conjugated oxo fatty acids. Thermal stability and gene expression analyses suggest that such covalent ligands are particularly effective activators of PPARγ and thus may serve as potent and biologically relevant ligands.
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Cites
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4318 · Cited by 2,164 · cited 1×
“Unsaturated fatty acids are more abundant than PGJ2 and have also been found to activate PPARγ, and hence they are candidate natural ligand”
BackgroundFat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085
Cited by
Varga, T., Czimmerer, Z., & Nagy, L. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.02.014 · Cited by 933
Self-citationStructural Overview of the Nuclear Receptor Superfamily: Insights into Physiology and Therapeutics
Huang, P., Chandra, V., & Rastinejad, F. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135917 · Cited by 533
Bazan, N. G., Molina, M. F., & Gordon, W. C. (2011) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104635 · Cited by 441
Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation
Serhan, C. N. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100322 · Cited by 421
Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors
Korbecki, J., Bobiński, R., & Dutka, M. (2019) · Inflammation Research · doi:10.1007/s00011-019-01231-1 · Cited by 415
Metadata
- Authors
- Itoh, T., Fairall, L., Amin, K., Inaba, Y., Szanto, A., Balint, B. L., Nagy, L., Yamamoto, K., & Schwabe, J. W. R.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2008-08-17
- Volume
- 15
- Issue
- 9
- Pages
- 924-931
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2066699861
- Cited by
- 457
- References
- 3
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Itoh, T., Fairall, L., Amin, K., Inaba, Y., Szanto, A., Balint, B. L., Nagy, L., Yamamoto, K., & Schwabe, J. W. R. (2008). Structural basis for the activation of PPARγ by oxidized fatty acids. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.1474
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