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Crystal structures of the human adiponectin receptors
- Source :
- Nature. April 16, 2015, p312, 16 p.
- Publication Year :
- 2015
-
Abstract
- Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G-protein-coupled receptors. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9 and 2.4 A resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity- related diseases, such as type 2 diabetes.<br />Adiponectin (encoded by ADIPOQ in humans) (1-4) is an anti-diabetic adipokine. Plasma adiponectin levels are reduced in obesity and type 2 diabetes (5), while the replenishment of adiponectin reportedly ameliorated [...]
Details
- Language :
- English
- ISSN :
- 00280836
- Database :
- Gale General OneFile
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.410142276
- Full Text :
- https://doi.org/10.1038/nature14301