View source for 9cbm


==Cryo-EM structure of dexmedetomidine-bound alpha-2A-adrenergic receptor in complex with heterotrimeric Gi-protein==
<StructureSection load='9cbm' size='340' side='right'caption='[[9cbm]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9cbm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [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/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9CBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CBM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</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=9cbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9cbm OCA], [https://pdbe.org/9cbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9cbm RCSB], [https://www.ebi.ac.uk/pdbsum/9cbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9cbm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Agonists targeting alpha(2)-adrenergic receptors (ARs) are used to treat diverse conditions, including hypertension, attention-deficit/hyperactivity disorder, pain, panic disorders, opioid and alcohol withdrawal symptoms, and cigarette cravings. These receptors transduce signals through heterotrimeric Gi proteins. Here, we elucidated cryo-EM structures that depict alpha(2A)-AR in complex with Gi proteins, along with the endogenous agonist epinephrine or the synthetic agonist dexmedetomidine. Molecular dynamics simulations and functional studies reinforce the results of the structural revelations. Our investigation revealed that epinephrine exhibits different conformations when engaging with alpha-ARs and beta-ARs. Furthermore, alpha(2A)-AR and beta(1)-AR (primarily coupled to Gs, with secondary associations to Gi) were compared and found to exhibit different interactions with Gi proteins. Notably, the stability of the epinephrine-alpha(2A)-AR-Gi complex is greater than that of the dexmedetomidine-alpha(2A)-AR-Gi complex. These findings substantiate and improve our knowledge on the intricate signaling mechanisms orchestrated by ARs and concurrently shed light on the regulation of alpha-ARs and beta-ARs by epinephrine.

Distinct binding conformations of epinephrine with alpha- and beta-adrenergic receptors.,Lou JS, Su M, Wang J, Do HN, Miao Y, Huang XY Exp Mol Med. 2024 Sep 2. doi: 10.1038/s12276-024-01296-x. PMID:39218975<ref>PMID:39218975</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 9cbm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Do HN]]
[[Category: Huang XY]]
[[Category: Lou JS]]
[[Category: Miao Y]]
[[Category: Su M]]
[[Category: Wang J]]