View source for 3kj6


==Crystal structure of a Methylated beta2 Adrenergic Receptor-Fab complex==
<StructureSection load='3kj6' size='340' side='right'caption='[[3kj6]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3kj6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KJ6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3kj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kj6 OCA], [https://pdbe.org/3kj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kj6 RCSB], [https://www.ebi.ac.uk/pdbsum/3kj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kj6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ADRB2_HUMAN ADRB2_HUMAN] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kj/3kj6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kj6 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor.,Bokoch MP, Zou Y, Rasmussen SG, Liu CW, Nygaard R, Rosenbaum DM, Fung JJ, Choi HJ, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS, Mueller L, Kobilka BK Nature. 2010 Jan 7;463(7277):108-12. PMID:20054398<ref>PMID:20054398</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3kj6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Bokoch MP]]
[[Category: Choi H-J]]
[[Category: Fung JJ]]
[[Category: Kobilka BK]]
[[Category: Kobilka TS]]
[[Category: Liu CW]]
[[Category: Mueller L]]
[[Category: Nygaard R]]
[[Category: Pardo L]]
[[Category: Prosser S]]
[[Category: Puglisi JD]]
[[Category: Rasmussen SGF]]
[[Category: Rosenbaum DM]]
[[Category: Thian FS]]
[[Category: Weis WI]]
[[Category: Zou Y]]