View source for 4ldo


==Structure of beta2 adrenoceptor bound to adrenaline and an engineered nanobody==
<StructureSection load='4ldo' size='340' side='right'caption='[[4ldo]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ldo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LDO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LDO 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WV:(2S)-2,3-DIHYDROXYPROPYL+(7Z)-TETRADEC-7-ENOATE'>1WV</scene>, <scene name='pdbligand=ALE:L-EPINEPHRINE'>ALE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4ldo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ldo OCA], [https://pdbe.org/4ldo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ldo RCSB], [https://www.ebi.ac.uk/pdbsum/4ldo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ldo 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.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
G-protein-coupled receptors (GPCRs) are integral membrane proteins that have an essential role in human physiology, yet the molecular processes through which they bind to their endogenous agonists and activate effector proteins remain poorly understood. So far, it has not been possible to capture an active-state GPCR bound to its native neurotransmitter. Crystal structures of agonist-bound GPCRs have relied on the use of either exceptionally high-affinity agonists or receptor stabilization by mutagenesis. Many natural agonists such as adrenaline, which activates the beta2-adrenoceptor (beta2AR), bind with relatively low affinity, and they are often chemically unstable. Using directed evolution, we engineered a high-affinity camelid antibody fragment that stabilizes the active state of the beta2AR, and used this to obtain crystal structures of the activated receptor bound to multiple ligands. Here we present structures of the active-state human beta2AR bound to three chemically distinct agonists: the ultrahigh-affinity agonist BI167107, the high-affinity catecholamine agonist hydroxybenzyl isoproterenol, and the low-affinity endogenous agonist adrenaline. The crystal structures reveal a highly conserved overall ligand recognition and activation mode despite diverse ligand chemical structures and affinities that range from 100 nM to approximately 80 pM. Overall, the adrenaline-bound receptor structure is similar to the others, but it has substantial rearrangements in extracellular loop three and the extracellular tip of transmembrane helix 6. These structures also reveal a water-mediated hydrogen bond between two conserved tyrosines, which appears to stabilize the active state of the beta2AR and related GPCRs.

Adrenaline-activated structure of beta2-adrenoceptor stabilized by an engineered nanobody.,Ring AM, Manglik A, Kruse AC, Enos MD, Weis WI, Garcia KC, Kobilka BK Nature. 2013 Oct 24;502(7472):575-9. doi: 10.1038/nature12572. Epub 2013 Sep 22. PMID:24056936<ref>PMID:24056936</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ldo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Enos MD]]
[[Category: Garcia KC]]
[[Category: Kobilka BK]]
[[Category: Kruse AC]]
[[Category: Manglik A]]
[[Category: Ring AM]]
[[Category: Weis WI]]