Sandbox Reserved 1100

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Revision as of 17:45, 14 January 2020

This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115.

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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, present in the blood at high concentration, approximatively 0,01 % of the total amount of proteins in plasma. 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. The hormone is mainly created by adipocytes present in white and brown adipose tissues but some studies manifest that it could be produced in some non-adipose tissues as in skeletal muscle. 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 (1oen) and carboxykinase1, involved in gluconeogenesis.

G protein-coupled receptor

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 contains an internal (residues 89 to 120), a short intracellular domain called (residues 121 to 129), (residues 134 to 364) and an external (residues 365 to 375).

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 and an external while the G-protein family has an internal N-terminus domain and an external C-terminus domain.

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 ??? protrude and are exposed too. The seven transmembrane helices surround 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 helices V and VI, and between the helices IV and VI. 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 helix VII. 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 helices II, III and VII 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. AdipoR1 has the capacity to form oligomers. 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 helix 5. 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 composed of residues 42 to 107 (plus loin dans l’article: 60 à 89…) 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.

Disease

References

↑ 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
↑ 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

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_1100"

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 The Adiponectin receptor 1 is an integral membrane protein composed of 375 amino acids and its molecular weight is 42,4 kDa. This protein contains an internal <scene name='82/829353/N-terminus_domain/1'>N-terminus domain</scene> (residues 89 to 120), a short intracellular domain called <scene name='82/829353/Helice0/1'>helix 0</scene> (residues 121 to 129), <scene name='82/829353/7tm/1'>seven transmembrane helices</scene> (residues 134 to 364) and an external <scene name='82/829353/C-terminus_domain/1'>C-terminus domain</scene> (residues 365 to 375).
-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/1'>N-terminus domain</scene> and an external <scene name='82/829353/C-terminus_domain/1'>C-terminus domain</scene> domain while the G-protein family has an internal N-terminus domain and an external C-terminus domain.
+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/1'>N-terminus domain</scene> and an external <scene name='82/829353/C-terminus_domain/1'>C-terminus domain</scene>  while the G-protein family has an internal N-terminus domain and an external C-terminus domain.
 The Adiponectin receptor 1 contains <scene name='82/829353/7tm/1'>seven transmembrane helices</scene> linked thanks to three extracellular loops and three intracellular loops. The <scene name='82/829353/Helix1/1'>helix I</scene> is formed by the residues 135 to 157, <scene name='82/829353/Helix2/1'>helix II</scene> by the residues 169 to 192, the <scene name='82/829353/Helix3/1'>helix III</scene> by the residues 198 to 227, the <scene name='82/829353/Helix4/1'>helix IV</scene> by the residues 232 to 252, the <scene name='82/829353/Helice5/1'>helix V</scene> by the residues 264 to 288 <scene name='82/829353/Helix6/1'>heliX VI</scene> by the residues 305 to 319 and the <scene name='82/829353/Helix7/1'>helix VII</scene> by the residues 336 to 364 .Besides, the <scene name='82/829353/Helix3/1'>helix III</scene> and <scene name='82/829353/Helix6/1'>heliX VI</scene> are longer than the other helices. These <scene name='82/829353/7tm/1'>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 C-terminus domain. Besides, helices III and IV are longer than the other helices and as a result the C-terminal two turns of the helix VII protrude and are exposed too.
+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/1'>C-terminus domain</scene>. Besides, <scene name='82/829353/Helix3/1'>helix III</scene> and the <scene name='82/829353/Helix6/1'>heliX VI</scene>are longer than the other helices and as a result the <scene name='82/829353/C-terminus_domain/1'>C-terminus domain</scene>  two turns of the ??? protrude and are exposed too.
 The seven transmembrane helices surround a large internal cavity where a <scene name='82/829353/Zinc-binding_site/1'>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 helices V and VI, and between the helices IV and VI. 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/H191/1'>H191</scene> in the helix II, <scene name='82/829353/H337/1'>H337</scene> and <scene name='82/829353/H341/1'>H341</scene> in the helix VII. 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 helices II, III and VII 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.

Sandbox Reserved 1100

From Proteopedia

Revision as of 17:45, 14 January 2020

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Disease

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