{{Sandbox_ESBS_2019}}
=='''The AdipoR1 receptor'''==
<StructureSection load='3wxv' size='340' side='right' caption='Caption for this structure' scene=''>
<ref>DOI 10.1002/ijch.201300024</ref>
<ref>PMID:21638687</ref>

== FUNCTION ==
The protein adiponectin receptor 1 is one of the two receptors for the hormone called adiponectin. The adiponectin is an hormone, and more precisely an adipokine <ref name="doc1">Tanabe, Hiroaki, Yoshifumi Fujii, Miki Okada-Iwabu, Masato Iwabu, Yoshihiro Nakamura, Toshiaki Hosaka, Kanna Motoyama, et al. « Crystal structures of the human adiponectin receptors ». Nature 520, nᵒ 7547 (1 avril 2015): 312‑16. https://doi.org/10.1038/nature14301</ref> <ref name="doc8">Kadowaki, Takashi et al. “Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.” The Journal of clinical investigation vol. 116,7 (2006): 1784-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483172/</ref>, present in the blood at high concentration, approximatively 0,01 % of the total amount of proteins in plasma<ref name="doc7">Whitehead, J. P., A. A. Richards, I. J. Hickman, G. A. Macdonald, et J. B. Prins. « Adiponectin – a Key Adipokine in the Metabolic Syndrome ». Diabetes, Obesity and Metabolism 8, nᵒ 3 (2006): 264‑80. https://doi.org/10.1111/j.1463-1326.2005.00510.x.</ref>. The human adiponectin monomer as molecular weight of about 28 kDa and is composed of 244 amino acids. However, the molecular weight of the hormone depends on the multimerization of this one <ref name="doc7"/>. The hormone is mainly created by adipocytes present in brown and white adipose tissues but according to researches it could also be produced in some non-adipose tissues as in skeletal muscle <ref name="doc7"/>. Two forms of adiponectin exist: the full-length adiponectin, presents in the liver and the globular adiponectin presents in skeletal muscles and in the liver. The adiponectin receptor 1 is a receptor for the globular form. This hormone is known to be anti-diabetic, antiatherogenic and a regulator of tissue inflammation and insulin sensitivity. These properties of the adiponectin are linked to the fatty oxidation trigger by the hormone and the adipoR1 receptor. Different fatty acid oxidation pathway exists. The major pathway regulated by adipoR1 is the AMP kinase channel, but this pathway is not completely known. However, several studies show that adipoR1 decreases the hepatic glucose production by activating this channel. AdipoR1 is also able to limit the expression of enzymes, like glucose-6-phosphatase, [[phosphoenolpyruvate carboxykinase]] and carboxykinase1, involved in gluconeogenesis.

== STRUCTURE ==

The Adiponectin receptor 1 is an integral membrane protein composed of 375 amino acids and its molecular weight is 42,4 kDa. This protein can be decomposed into different parts: an internal <scene name='82/829353/N-terminus_domain/2'>N-terminus domain</scene> (residues 89 to 120), a short intracellular domain called <scene name='82/829353/Helice0/2'>helix 0</scene> (residues 121 to 129), <scene name='82/829353/7helices/1'>seven transmembrane helices</scene> (residues 134 to 364) and an external <scene name='82/829353/C-terminus_domain/3'>C-terminus domain</scene> (residues 365 to 375). <ref name="doc1"/>

The organisation of the structure of the Adiponectin receptor 1 is the opposite to [[G protein-coupled receptor]] family. Indeed, the Adiponectin receptor has an internal <scene name='82/829353/N-terminus_domain/2'>N-terminus domain</scene> and an external <scene name='82/829353/C-terminus_domain/3'>C-terminus domain</scene> while the G-protein family has an internal N-terminus domain and an external C-terminus domain. <ref name="doc3"> Takashi Kadowaki and Toshimasa Yamauchi et al. « Adiponectin and adiponectin receptors». https://www.ncbi.nlm.nih.gov/pubmed/15897298</ref>
The Adiponectin receptor 1 contains <scene name='82/829353/7helices/1'>seven transmembrane helices</scene> linked thanks to three extracellular loops and three intracellular loops. The <scene name='82/829353/Helix1/2'>helix I</scene> is formed by the residues 135 to 157, <scene name='82/829353/Helix2/2'>helix II</scene> by the residues 169 to 192, the <scene name='82/829353/Helix3/2'>helix III</scene> by the residues 198 to 227, the <scene name='82/829353/Helix4/2'>helice IV</scene> by the residues 232 to 252, the <scene name='82/829353/Helice5/2'>helix V</scene> by the residues 264 to 288 <scene name='82/829353/Helix6/2'>heliX VI</scene> by the residues 305 to 319 and the <scene name='82/829353/Helix7/2'>helix VII</scene> by the residues 336 to 364 .Besides, the <scene name='82/829353/Helix3/2'>helix III</scene> and <scene name='82/829353/Helix7/2'>VII</scene> are longer than the other helices. These <scene name='82/829353/7tm/2'>seven transmembrane helices</scene> have a clockwise circular specific organisation (from helix I to helix VII) and form a bundle.
Concerning the extracellular faces, the three extracellular loops which connect the transmembrane helices are exposed and it is the same for the <scene name='82/829353/C-terminus_domain/3'>C-terminus domain</scene>. Besides, <scene name='82/829353/Helix3/2'>helix III</scene> and the <scene name='82/829353/Helix7/2'>VII</scene> are longer than the other helices and as a result the <scene name='82/829353/C-terminus_domain/3'>C-terminus domain</scene> two turns of the <scene name='82/829353/Helix7/2'>VII</scene> are exposed too. <ref name="doc1">Tanabe, Hiroaki, Yoshifumi Fujii, Miki Okada-Iwabu, Masato Iwabu, Yoshihiro Nakamura, Toshiaki Hosaka, Kanna Motoyama, et al. « Crystal structures of the human adiponectin receptors ». Nature 520, nᵒ 7547 (1 avril 2015): 312‑16. https://doi.org/10.1038/nature14301</ref>
In the middle of the seven transmembrane helices there is a large internal cavity where a <scene name='82/829353/Zinc-binding_site/2'>zinc-binding site</scene> can be found. This cavity located from the cytoplasmic surface to the middle of the outer lipid layer of the membrane has small openings between the <scene name='82/829353/Helice5/2'>helix V</scene> and <scene name='82/829353/Helix6/2'>VI</scene>, and between the <scene name='82/829353/Helix4/2'>helice IV</scene> and <scene name='82/829353/Helix6/2'>VI</scene>. It has been assumed that these openings are involved in the entrance and exit of both substrate and product.
In this cavity, there is a zinc ion which is coordinated thanks to three histidine residues. These three histidine residues are <scene name='82/829353/H191/2'>H191</scene> in the helix II, <scene name='82/829353/H337/2'>H337</scene> and <scene name='82/829353/H341/2'>H341</scene> in the <scene name='82/829353/Helix7/2'>helix VII</scene>. As a result, the zinc ion is in the intracellular layer of the membrane, in the neighbourhood of 4° deep from the inner surface of the plasma membrane. Thanks to its tetrahedral coordination, this zinc ion binds the <scene name='82/829353/Helix2/2'>helix II</scene>, <scene name='82/829353/Helix3/2'>III</scene> and <scene name='82/829353/Helix7/2'>VII</scene> together. The adiponectin-stimulated AMPK phosphorylation doesn’t directly require the zinc binding site, nevertheless it has been supposed that the zinc ion allows a stabilizing effect. <ref name="doc1">Tanabe, Hiroaki, Yoshifumi Fujii, Miki Okada-Iwabu, Masato Iwabu, Yoshihiro Nakamura, Toshiaki Hosaka, Kanna Motoyama, et al. « Crystal structures of the human adiponectin receptors ». Nature 520, nᵒ 7547 (1 avril 2015): 312‑16. https://doi.org/10.1038/nature14301</ref>
AdipoR1 has the capacity to form oligomers. <ref name="doc3"> Takashi Kadowaki and Toshimasa Yamauchi et al. « Adiponectin and adiponectin receptors». https://www.ncbi.nlm.nih.gov/pubmed/15897298</ref> Indeed in living cell both monomers and oligomers are present. A specific motif was identified to contribute to the AdipoR1 dimerization: it is the motif GxxxG in the transmembrane <scene name='82/829353/Helice5/2'>helix V</scene>. Besides, the dimerization of AdipoR1 is also regulated. This dimerization is inhibited by the fixation of the full-length adiponectin while the globular adiponectin has any impact on the dimerization level of the AdipoR1 receptor. Thanks to mutant experiment, it can be supposed that the collagen-like domain of the full-length adiponectin is responsible to the dimer dissociation. There are strong evidences that dimerization of the AdipoR1 receptor has a role during the biosynthesis, the trafficking and the signalling of the seven transmembrane receptors. <ref name="doc4"> Kosel D, Heiker JT, Juhl C, Wottawah CM, Blüher M, Mörl K, Beck-Sickinger AG et al. « Dimerization of adiponectin 1 is inhibited by adiponectin » Journal of Cell Science 123, 1320-1328 : https://www.ncbi.nlm.nih.gov/pubmed/20332107</ref>

== Diseases ==

</StructureSection>

== References ==
<references/>