7ejk | pdb_00007ejk

Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to oxymetazoline

spinqualitylabelsall models 7ejk, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ejk is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: J5C Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNAO_HUMAN Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function GNAO_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14. Publication Abstract from PubMed The alpha(2A) adrenergic receptor (alpha(2A)AR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human alpha(2A)AR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the alpha(2A)AR. Further structural analyses uncover different molecular determinants between alpha(2A)AR and betaARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for alpha(2A)AR. Structural insights into ligand recognition, activation, and signaling of the alpha(2A) adrenergic receptor.,Xu J, Cao S, Hubner H, Weikert D, Chen G, Lu Q, Yuan D, Gmeiner P, Liu Z, Du Y Sci Adv. 2022 Mar 4;8(9):eabj5347. doi: 10.1126/sciadv.abj5347. Epub 2022 Mar 4. PMID:35245122 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures Transducin 3D structures

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