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== FUNCTION ==
== FUNCTION ==
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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"/><ref name="doc8"/>.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 sensitive in particular to the globular form<ref name="doc8"/>. This hormone is known to be anti-diabetic, antiatherogenic and a regulator of tissue inflammation and insulin sensitivity<ref name="doc9">Yamauchi, Toshimasa, Junji Kamon, Yusuke Ito, Atsushi Tsuchida, Takehiko Yokomizo, Shunbun Kita, Takuya Sugiyama, et al. « Cloning of adiponectin receptors that mediate antidiabetic metabolic effects ». Nature 423, nᵒ 6941 (1 juin 2003): 762‑69. https://doi.org/10.1038/nature01705.</ref>. 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.
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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"/><ref name="doc8"/>.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 sensitive in particular to the globular form<ref name="doc8"/>. This hormone is known to be anti-diabetic, antiatherogenic and a regulator of tissue inflammation and insulin sensitivity<ref name="doc9">Yamauchi, Toshimasa, Junji Kamon, Yusuke Ito, Atsushi Tsuchida, Takehiko Yokomizo, Shunbun Kita, Takuya Sugiyama, et al. « Cloning of adiponectin receptors that mediate antidiabetic metabolic effects ». Nature 423, nᵒ 6941 (1 juin 2003): 762‑69. https://doi.org/10.1038/nature01705.</ref>. 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<ref name="doc9">Capeau, Jacqueline. « The Story of Adiponectin and Its Receptors AdipoR1 and R2: To Follow ». Journal of Hepatology 47, nᵒ 5 (1 novembre 2007): 736‑38. https://doi.org/10.1016/j.jhep.2007.06.002.</ref>

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The AdipoR1 receptor

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References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ 3.0 3.1 3.2 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
  4. ↑ 4.0 4.1 4.2 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/
  5. ↑ 5.0 5.1 5.2 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.
  6. ↑ 6.0 6.1 Yamauchi, Toshimasa, Junji Kamon, Yusuke Ito, Atsushi Tsuchida, Takehiko Yokomizo, Shunbun Kita, Takuya Sugiyama, et al. « Cloning of adiponectin receptors that mediate antidiabetic metabolic effects ». Nature 423, nᵒ 6941 (1 juin 2003): 762‑69. https://doi.org/10.1038/nature01705.
  7. ↑ Takashi Kadowaki and Toshimasa Yamauchi et al. « Adiponectin and adiponectin receptors». https://www.ncbi.nlm.nih.gov/pubmed/15897298
  8. ↑ Parker-Duffen JL, Nakamura K, Silver M, Zuriaga MA, MacLauchlan S, Aprahamian TR, Walsh K et al. «Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo.» 17 April 2014 : https://www.ncbi.nlm.nih.gov/pubmed/24742672 /> The Adiponectin receptor 1 contains linked thanks to three extracellular loops and three intracellular loops. The is formed by the residues 135 to 157, by the residues 169 to 192, the by the residues 198 to 227, the by the residues 232 to 252, the by the residues 264 to 288 by the residues 305 to 319 and the by the residues 336 to 364 .Besides, the and are longer than the other helices. These 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 . Besides, and the are longer than the other helices and as a result the two turns of the are exposed too. <ref></ref> In the middle of the seven transmembrane helices there is a large internal cavity where a 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 and , and between the and . 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 in the helix II, and in the . 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 , and 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></ref> AdipoR1 has the capacity to form oligomers. <ref> Takashi Kadowaki and Toshimasa Yamauchi et al. « Adiponectin and adiponectin receptors». https://www.ncbi.nlm.nih.gov/pubmed/15897298</li> <li id="cite_note-doc4-8">[[#cite_ref-doc4_8-0|↑]] 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</li></ol></ref>
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