A collaboration led by Dr. Shigeyuki Yokoyama of RIKEN and Dr. Takashi Kadowaki and Dr. Toshimasa Yamauchi of the University of Tokyo has used the SPring-8 synchrotron facility (photo) in Harima, Japan to elucidate the structure of two receptors for adiponectin, a protein that is associated with obesity and diabetes. The researchers hope that in the future this work, which was published in Nature on April 8, 2015, will pave the way toward designing drugs that target these two receptors, AdipoR1 and AdipoR2, to reduce the early mortality associated with diabetes. Adiponectin, a hormone secreted by fat cells, is known to be involved in the regulation of glucose and fatty acid oxidation. Its levels are reduced in patients with both type 1 and type 2 diabetes, and giving the hormone to mice has been reported to improve glucose intolerance. In addition, administration of a recently discovered adiponectin receptor agonist, AdipoRon, to genetically obese mice led to improved glucose intolerance and longer lifespans. Because adiponectin binds to two receptors, AdipoR1 and AdipoR2, Dr. Yokoyama, who leads the RIKEN Structural Biology Laboratory, and his team surmised that understanding how this binding takes place could contribute to the creation of drugs that target these receptors. Adiponectin receptors are evolutionarily conserved in many living beings, including mammals, plants, and yeasts, so it seemed clear that these molecules should play important biological role(s). Using the microfocus beamline at the SPring-8 synchrotron facility, the group obtained crystallographic images of the two receptors at resolutions of just 2.9 and 2.4 angstroms, and came up with a surprising finding.
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