6e67
Structure of beta2 adrenergic receptor fused to a Gs peptideStructure of beta2 adrenergic receptor fused to a Gs peptide
Structural highlights
DiseaseGNAS2_HUMAN Pseudopseudohypoparathyroidism;Pseudohypoparathyroidism type 1A;Progressive osseous heteroplasia;Polyostotic fibrous dysplasia;Monostotic fibrous dysplasia;Pseudohypoparathyroidism type 1C;Pseudohypoparathyroidism type 1B;McCune-Albright syndrome. 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. 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. 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. The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed. 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. FunctionA0A097J809_BPT4 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.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).[1] [2] [3] [4] [5] Publication Abstract from PubMedThe crystal structure of the beta2-adrenergic receptor (beta2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (beta2AR-Gs(empty)). Unfortunately, the beta2AR-Gs(empty) complex does not provide a clear explanation for G protein coupling specificity. Evidence from several sources suggests the existence of a transient complex between the beta2AR and GDP-bound Gs protein (beta2AR-Gs(GDP)) that may represent an intermediate on the way to the formation of beta2AR-Gs(empty) and may contribute to coupling specificity. Here we present a structure of the beta2AR in complex with the carboxyl terminal 14 amino acids from Galphas along with the structure of the GDP-bound Gs heterotrimer. These structures provide evidence for an alternate interaction between the beta2AR and Gs that may represent an intermediate that contributes to Gs coupling specificity. Structural Insights into the Process of GPCR-G Protein Complex Formation.,Liu X, Xu X, Hilger D, Aschauer P, Tiemann JKS, Du Y, Liu H, Hirata K, Sun X, Guixa-Gonzalez R, Mathiesen JM, Hildebrand PW, Kobilka BK Cell. 2019 May 16;177(5):1243-1251.e12. doi: 10.1016/j.cell.2019.04.021. Epub, 2019 May 9. PMID:31080070[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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