How PPAR-gamma -- a fatty acid receptor that plays a central role in energy metabolism -- is activated by a natural ligand is revealed in a study online in Nature Structural & Molecular Biology. The findings could be useful in the design of better drugs to treat type 2 diabetes.
Dysfunctions in PPAR-gamma are linked to diabetes, cardiovascular disease and obesity, so the receptor is an important target for type 2 diabetes drugs. Previous work had shown that synthetic binding molecules, or ligands, activate PPAR-gamma by making contacts with one specific part of the protein.
Yong Li, Eric Xu and colleagues now show that nitrated linoleic acid, a potent natural ligand, makes contacts with this same region but also with a second one, explaining how it is recognized by PPAR-gamma and why it has such high activity.
H. Eric Xu (Van Andel Research Institute, Grand Rapids, MI, USA)
Yong Li (University of Pittsburgh, Pittsburgh, PA, USA)
Abstract available online.
(C) Nature Structural & Molecular Biology press release.
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