Sandbox Reserved 1095: Difference between revisions

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== History ==
== History ==
=== Discovery of angiotensin receptors===
=== Discovery of angiotensin receptors===
Researchers suspected since 70s the existence of different angiotensin receptors. However, tools to identify those distinct trans-membrane receptors became available ten years later. Receptors binding assays identified angiotensin receptors in vitro using radioactive angiotensin. Results showed several types of  angiotensin receptors, found in different tissues. The main receptors are AT1 and [https://en.wikipedia.org/wiki/Angiotensin_II_receptor_type_2 AT2] <ref>PMID:10821350</ref>.
Researchers had suspicions since the 1970s about the existence of different angiotensin receptors. However, tools to identify those distinct trans-membrane receptors became available only a decade later. Receptors binding assays identified angiotensin receptors in vitro using radioactive angiotensin. Results showed several types of  angiotensin receptors, found in different tissues. The main receptors are AT1 and [https://en.wikipedia.org/wiki/Angiotensin_II_receptor_type_2 AT2] <ref>PMID:10821350</ref>.


=== Nomenclature ===
=== Nomenclature ===
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=== Recent studies ===
=== Recent studies ===
Finally, around 2015, researchers have found the crystal structure of the receptor in complex with its antagonist [https://pubchem.ncbi.nlm.nih.gov/compound/ZD-7155-hydrochloride ZD7155] and with an inverse agonist [https://en.wikipedia.org/wiki/Olmesartan olmesartan]<ref> PMID: 26420482 </ref>. [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray cryogenic-crystallography] has been used. They have found similar conformation of the receptor when it is linked to the antagonist or to the inverse agonist. They have also found conserved molecular recognition modes. To complete this, they have performed mutagenesis experiments and managed to identify several residues in interaction with the ligand.
Around 2015, researchers found the crystal structure of the receptor in complex with its antagonist [https://pubchem.ncbi.nlm.nih.gov/compound/ZD-7155-hydrochloride ZD7155] and with an inverse agonist [https://en.wikipedia.org/wiki/Olmesartan olmesartan]<ref> PMID: 26420482 </ref>. [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray cryogenic-crystallography] has been used. They found similar conformation of the receptor when it is linked to the antagonist or to the inverse agonist. They have also found conserved molecular recognition modes. To complete this, they have performed mutagenesis experiments and managed to identify several residues in interaction with the ligand.
The structure of this protein have also been solved in 2017 using an other method called serial femtosecond crystallography, corresponding to the structure [http://proteopedia.org/wiki/index.php/4yay 4YAY] <ref name="Zhang2017">PMID:25913193</ref>.
The structure of this protein was solved in 2017 using another method called serial femtosecond crystallography, corresponding to the structure [http://proteopedia.org/wiki/index.php/4yay 4YAY] <ref name="Zhang2017">PMID:25913193</ref>.


== Structure (function relationship) ==
== Structure (function relationship) ==


=== Primary and secondary structure ===
=== Primary and secondary structure ===
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 of 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 α helix</scene>
<scene name='82/829348/Helix_a/1'>18 α helix</scene>
and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 α 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 α helical trans-membrane protein.
and <scene name='82/829348/B_sheet/1'>3 β sheets</scene>. Moreover, 7 α helixes are made of a majority of hydrophobic amino acids. These helixes 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 α helical trans-membrane protein.
Since the angiotensin receptor belongs to the GPCRs family, those 7 α helix contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.
Since the angiotensin receptor belongs to the GPCRs family, those 7 α helixes contain 3 extracellular and 3 intracellular loops. The N terminus corresponds to the extracellular domain. The C terminal domain is located intracellularly.


=== Ligand binding pocket ===
=== Ligand binding pocket ===
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