4bvn
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bvn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Meleagris_gallopavo Meleagris gallopavo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BVN FirstGlance]. <br> | <table><tr><td colspan='2'>[[4bvn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Meleagris_gallopavo Meleagris gallopavo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BVN FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MHA:(CARBAMOYLMETHYL-CARBOXYMETHYL-AMINO)-ACETIC+ACID'>MHA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P32:4-{[(2S)-3-(TERT-BUTYLAMINO)-2-HYDROXYPROPYL]OXY}-3H-INDOLE-2-CARBONITRILE'>P32</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]] 2.1Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MHA:(CARBAMOYLMETHYL-CARBOXYMETHYL-AMINO)-ACETIC+ACID'>MHA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P32:4-{[(2S)-3-(TERT-BUTYLAMINO)-2-HYDROXYPROPYL]OXY}-3H-INDOLE-2-CARBONITRILE'>P32</scene></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=4bvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvn OCA], [https://pdbe.org/4bvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bvn RCSB], [https://www.ebi.ac.uk/pdbsum/4bvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvn 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=4bvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvn OCA], [https://pdbe.org/4bvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bvn RCSB], [https://www.ebi.ac.uk/pdbsum/4bvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvn ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/ADRB1_MELGA ADRB1_MELGA] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. | |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The beta1-adrenoceptor (beta1AR) is a G protein-coupled receptor (GPCR) that is activated by the endogenous agonists adrenaline and noradrenaline. We have determined the structure of an ultra-thermostable beta1AR mutant bound to the weak partial agonist cyanopindolol to 2.1 A resolution. High-quality crystals (100 mum plates) were grown in lipidic cubic phase without the assistance of a T4 lysozyme or BRIL fusion in cytoplasmic loop 3, which is commonly employed for GPCR crystallisation. An intramembrane Na+ ion was identified co-ordinated to Asp872.50, Ser1283.39 and 3 water molecules, which is part of a more extensive network of water molecules in a cavity formed between transmembrane helices 1, 2, 3, 6 and 7. Remarkably, this water network and Na+ ion is highly conserved between beta1AR and the adenosine A2A receptor (rmsd of 0.3 A), despite an overall rmsd of 2.4 A for all Calpha atoms and only 23% amino acid identity in the transmembrane regions. The affinity of agonist binding and nanobody Nb80 binding to beta1AR is unaffected by Na+ ions, but the stability of the receptor is decreased by 7.5 degrees C in the absence of Na+. Mutation of amino acid side chains that are involved in the co-ordination of either Na+ or water molecules in the network decreases the stability of beta1AR by 5-10 degrees C. The data suggest that the intramembrane Na+ and associated water network stabilise the ligand-free state of beta1AR, but still permits the receptor to form the activated state which involves the collapse of the Na+ binding pocket on agonist binding. | ||
| + | |||
| + | The 2.1 A Resolution Structure of Cyanopindolol-Bound beta1-Adrenoceptor Identifies an Intramembrane Na+ Ion that Stabilises the Ligand-Free Receptor.,Miller-Gallacher JL, Nehme R, Warne T, Edwards PC, Schertler GF, Leslie AG, Tate CG PLoS One. 2014 Mar 24;9(3):e92727. doi: 10.1371/journal.pone.0092727. eCollection, 2014. PMID:24663151<ref>PMID:24663151</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4bvn" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]] | *[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Ultra-thermostable beta1-adrenoceptor with cyanopindolol bound
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