9cbl

Cryo-EM structure of epinephrine-bound alpha-2A-adrenergic receptor in complex with heterotrimeric Gi-protein

spinqualitylabelsall models 9cbl, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9cbl is a 4 chain structure with sequence from Bos taurus, Escherichia virus T4, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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