Crystal structures of the human adiponectin receptors

DOI: 10.1038/nature14301
PMID: 25855295

Authors: Hiroaki Tanabe (RIKEN) , Yoshifumi Fujii (RIKEN) , Miki Okada-Iwabu (University of Tokyo) , Masato Iwabu (University of Tokyo) , Yoshihiro Nakamura (RIKEN) , Toshiaki Hosaka (RIKEN) , Kanna Motoyama (RIKEN) , Mariko Ikeda (RIKEN) , Motoaki Wakiyama (RIKEN) , Takaho Terada (RIKEN) , Noboru Ohsawa (RIKEN) , Masakatsu Hato (RIKEN) , Satoshi Ogasawara (Kyoto University) , Tomoya Hino (Kyoto University) , Takeshi Murata (RIKEN) , So Iwata (Diamond Light Source; RIKEN) , Kunio Hirata (RIKN) , Yoshiaki Kawano (RIKEN) , Masaki Yamamoto (RIKEN) , Tomomi Kimura-Someya (RIKEN)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 520 , PAGES 312 - 316

State: Published (Approved)
Published: April 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 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.

Diamond Keywords: Obesity; Diabetes; Type 2 Diabetes

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Membrane Protein Laboratory (MPL)
Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: BL32XU at SPring-8; X06SA at SLS

Added On: 12/01/2016 15:53

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)