Sandbox Reserved 1095: Difference between revisions

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AT1 receptor consists in a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of
AT1 receptor consists in a 376 amino acid string <ref> [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4zud&template=main.html Protein Database (PDBsum): 4zud. European Bioinformatics (EBI); 2013.]</ref>. The protein is composed of
<scene name='82/829348/Helix_a/1'>18 alpha helix</scene>
<scene name='82/829348/Helix_a/1'>18 alpha helix</scene>
and <scene name='82/829348/B_sheet/1'>3 beta helix</scene>. Moreover, 7 alpha helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an alpha helical trans-membrane protein.
and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 alpha helix are made of a majority of hydrophobic amino acids. These helix are long enough to cross the membrane and create an <scene name='82/829348/Transmambrane_protein/1'>hydrophobic domain</scene> which is situated into the membrane. The human angiotensin receptor is therefore an alpha helical trans-membrane protein.
Since the angiotensin receptor belongs to the GPCRs family, those 7 alpha helix contain 3 extracellular and 3 intracellular loops.  
Since the angiotensin receptor belongs to the GPCRs family, those 7 alpha helix contain 3 extracellular and 3 intracellular loops.  
The N terminus corresponds to the extracellular domain. The protein is made of three intracellular loops and three extracellular loops. The C terminal domain is located intracellularly.
The N terminus corresponds to the extracellular domain. The protein is made of three intracellular loops and three extracellular loops. The C terminal domain is located intracellularly.


=== Ligand binding pocket ===
=== Ligand binding pocket ===
In the extracellular environment, there is a beta-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 alpha helix which create a gate between the membrane and the extracellular environment.  
In the extracellular environment, there is a β-hairpin in conjugation with <scene name='82/829348/Disulfuric_bridge/1'>two extracellular disulfure bridges</scene>. This structure is responsible for the opening and the locking of the ligand binding pocket <ref> PMID: 23386604  </ref>. The ligand goes into an <scene name='82/829348/Ligand_blinding_pocket/1'>hydrophilic pocket</scene> created into the membrane thanks to the 7 alpha helix which create a gate between the membrane and the extracellular environment.  


AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/1'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helices and in interaction between TM2 and TM7.  
AngII mediates AT1 receptor activation via stacking interactions between Phe8(AngII)/<scene name='82/829348/His_256/2'>His256</scene>(AT1 receptor) and Tyr4(AngII)/<scene name='82/829348/Asn_111/1'>Asn111</scene>(AT1 receptor). This phenomenon results in a conformational change in transmembrane (TM)3-TM6 helices and in interaction between TM2 and TM7.  


=== G protein-binding site ===
=== G protein-binding site ===
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=== Interaction with other GPCRs ===
=== Interaction with other GPCRs ===


It has been discovered that AT1Rs were also able to bind with other GPCRs to form homo- or heterodimers. Those interactions can modify the sensitivity of the receptor, which leads to different physiological and pathological conditions than the GPCR monomer <ref name="Zhang2015"/> <ref name="Takanobu2017">PMID:28648738 </ref>. The most known heterodimers including AT1 receptor are with [[Beta-2 adrenergic receptor]], [https://en.wikipedia.org/wiki/Apelin_receptor the apelin receptor] ([[5vbl]]), and AT2 receptor. Those interactions could be facilitated by several transmembrane domains.
It has been discovered that AT1Rs were also able to bind with other GPCRs to form homo- or heterodimers. Those interactions can modify the sensitivity of the receptor, which leads to different physiological and pathological conditions than the GPCR monomer <ref name="Zhang2015"/> <ref name="Takanobu2017">PMID:28648738 </ref>. The most known heterodimers including AT1 receptor are with [[β2 adrenergic receptor]], [https://en.wikipedia.org/wiki/Apelin_receptor the apelin receptor] ([[5vbl]]), and AT2 receptor. Those interactions could be facilitated by several transmembrane domains.


The oligomeric complexes' formation complicate the understanding of AT1R pharmacology.
The oligomeric complexes' formation complicate the understanding of AT1R pharmacology.
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