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| | <StructureSection load='6os0' size='340' side='right'caption='[[6os0]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='6os0' size='340' side='right'caption='[[6os0]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6os0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OS0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6os0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OS0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGTR1, AGTR1A, AGTR1B, AT2R1, AT2R1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6os0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6os0 OCA], [http://pdbe.org/6os0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6os0 RCSB], [http://www.ebi.ac.uk/pdbsum/6os0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6os0 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6os0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6os0 OCA], [https://pdbe.org/6os0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6os0 RCSB], [https://www.ebi.ac.uk/pdbsum/6os0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6os0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN]] NON RARE IN EUROPE: Essential hypertension;Renal tubular dysgenesis of genetic origin. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:[http://omim.org/entry/145500 145500]]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause. Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:[http://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref> | + | [https://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN] NON RARE IN EUROPE: Essential hypertension;Renal tubular dysgenesis of genetic origin. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN]] Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. [[http://www.uniprot.org/uniprot/ANGT_HUMAN ANGT_HUMAN]] Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-2: acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin-3: stimulates aldosterone release.<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).<ref>PMID:1132082</ref> <ref>PMID:10619573</ref> <ref>PMID:17138938</ref> | + | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN] Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Kleinhenz, A L.W]] | + | [[Category: Kleinhenz ALW]] |
| - | [[Category: Kruse, A C]] | + | [[Category: Kruse AC]] |
| - | [[Category: Lefkowitz, R J]] | + | [[Category: Lefkowitz RJ]] |
| - | [[Category: McMahon, C]] | + | [[Category: McMahon C]] |
| - | [[Category: Skiba, M A]] | + | [[Category: Skiba MA]] |
| - | [[Category: Staus, D P]] | + | [[Category: Staus DP]] |
| - | [[Category: Wingler, L M]] | + | [[Category: Wingler LM]] |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Nanobody]]
| + | |
| Structural highlights
Disease
AGTR1_HUMAN NON RARE IN EUROPE: Essential hypertension;Renal tubular dysgenesis of genetic origin. The disease is caused by mutations affecting the gene represented in this entry.
Function
C562_ECOLX Electron-transport protein of unknown function.AGTR1_HUMAN Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Publication Abstract from PubMed
Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly beta-arrestin-biased analogs. Compared with other ligands, AngII promotes more-substantial rearrangements not only at the bottom of the ligand-binding pocket but also in a key polar network in the receptor core, which forms a sodium-binding site in most GPCRs. Divergences from the family consensus in this region, which appears to act as a biased signaling switch, may predispose the AT1R and certain other GPCRs (such as chemokine receptors) to adopt conformations that are capable of activating beta-arrestin but not heterotrimeric Gq protein signaling.
Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.,Wingler LM, Skiba MA, McMahon C, Staus DP, Kleinhenz ALW, Suomivuori CM, Latorraca NR, Dror RO, Lefkowitz RJ, Kruse AC Science. 2020 Feb 21;367(6480):888-892. doi: 10.1126/science.aay9813. PMID:32079768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wingler LM, Skiba MA, McMahon C, Staus DP, Kleinhenz ALW, Suomivuori CM, Latorraca NR, Dror RO, Lefkowitz RJ, Kruse AC. Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR. Science. 2020 Feb 21;367(6480):888-892. doi: 10.1126/science.aay9813. PMID:32079768 doi:http://dx.doi.org/10.1126/science.aay9813
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