8thl
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/GNAI2_HUMAN GNAI2_HUMAN] 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. May play a role in cell division.<ref>PMID:17635935</ref> Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.<ref>PMID:17550964</ref> [https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref> [https://www.uniprot.org/uniprot/GNAQ_HUMAN GNAQ_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (By similarity). | [https://www.uniprot.org/uniprot/GNAI2_HUMAN GNAI2_HUMAN] 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. May play a role in cell division.<ref>PMID:17635935</ref> Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.<ref>PMID:17550964</ref> [https://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref> [https://www.uniprot.org/uniprot/GNAQ_HUMAN GNAQ_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | alpha(1)-adrenergic receptors (alpha(1)-ARs) play critical roles in the cardiovascular and nervous systems where they regulate blood pressure, cognition, and metabolism. However, the lack of specific agonists for all alpha(1) subtypes has limited our understanding of the physiological roles of different alpha(1)-AR subtypes, and led to the stagnancy in agonist-based drug development for these receptors. Here we report cryo-EM structures of alpha(1A)-AR in complex with heterotrimeric G-proteins and either the endogenous common agonist epinephrine or the alpha(1A)-AR-specific synthetic agonist A61603. These structures provide molecular insights into the mechanisms underlying the discrimination between alpha(1A)-AR and alpha(1B)-AR by A61603. Guided by the structures and corresponding molecular dynamics simulations, we engineer alpha(1A)-AR mutants that are not responsive to A61603, and alpha(1B)-AR mutants that can be potently activated by A61603. Together, these findings advance our understanding of the agonist specificity for alpha(1)-ARs at the molecular level, opening the possibility of rational design of subtype-specific agonists. | ||
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| + | Structural basis of agonist specificity of alpha(1A)-adrenergic receptor.,Su M, Wang J, Xiang G, Do HN, Levitz J, Miao Y, Huang XY Nat Commun. 2023 Aug 10;14(1):4819. doi: 10.1038/s41467-023-40524-2. PMID:37563160<ref>PMID:37563160</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8thl" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Cryo-EM structure of epinephrine-bound alpha-1A-adrenergic receptor in complex with heterotrimeric Gq-protein
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