Crystal structures of the human adiponectin receptors

Hiroaki Tanabe, Yoshifumi Fujii, Miki Okada-Iwabu, Masato Iwabu, Yoshihiro Nakamura, Toshiaki Hosaka, Kanna Motoyama, Mariko Ikeda, Motoaki Wakiyama, Takaho Terada, Noboru Ohsawa, Masakatsu Hato, Satoshi Ogasawara, Tomoya Hino, Takeshi Murata, So Iwata, Kunio Hirata, Yoshiaki Kawano, Masaki Yamamoto, Tomomi Kimura-Someya, Mikako Shirouzu, Toshimasa Yamauchi (), Takashi Kadowaki () and Shigeyuki Yokoyama ()
Additional contact information
Hiroaki Tanabe: RIKEN Systems and Structural Biology Center
Yoshifumi Fujii: RIKEN Systems and Structural Biology Center
Miki Okada-Iwabu: Graduate School of Medicine, The University of Tokyo
Masato Iwabu: Graduate School of Medicine, The University of Tokyo
Yoshihiro Nakamura: RIKEN Systems and Structural Biology Center
Toshiaki Hosaka: RIKEN Systems and Structural Biology Center
Kanna Motoyama: RIKEN Systems and Structural Biology Center
Mariko Ikeda: RIKEN Systems and Structural Biology Center
Motoaki Wakiyama: RIKEN Systems and Structural Biology Center
Takaho Terada: RIKEN Systems and Structural Biology Center
Noboru Ohsawa: RIKEN Systems and Structural Biology Center
Masakatsu Hato: RIKEN Systems and Structural Biology Center
Satoshi Ogasawara: Graduate School of Medicine, Kyoto University
Tomoya Hino: Graduate School of Medicine, Kyoto University
Takeshi Murata: RIKEN Systems and Structural Biology Center
So Iwata: RIKEN Systems and Structural Biology Center
Kunio Hirata: RIKEN SPring-8 Center, Harima Institute
Yoshiaki Kawano: RIKEN SPring-8 Center, Harima Institute
Masaki Yamamoto: RIKEN SPring-8 Center, Harima Institute
Tomomi Kimura-Someya: RIKEN Systems and Structural Biology Center
Mikako Shirouzu: RIKEN Systems and Structural Biology Center
Toshimasa Yamauchi: Graduate School of Medicine, The University of Tokyo
Takashi Kadowaki: Graduate School of Medicine, The University of Tokyo
Shigeyuki Yokoyama: RIKEN Systems and Structural Biology Center

Nature, 2015, vol. 520, issue 7547, 312-316

Abstract: 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 Å 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.

Date: 2015
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DOI: 10.1038/nature14301

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