Human beta2-adrenergic receptor is one of the most studied G-protein-coupled receptors. It plays a key role in autonomic nervous system and is a drug target in cardiovascular and pulmonary diseases. Despite the fact that its crystal structure was revealed, a physiological role and molecular mechanisms of its action remain largely unknown. We designed the construct pVR2ADRH, which contained the gene for human beta2-adrenergic receptor with a polyhistidine tag C-terminal extension. The recombinant DNA was used for transformation of the GS115 strain of Pichia pastoris. The heterologous expression level obtained was about 20 mg/l. The receptor was extracted from membrane fraction and was purified by metal-affinity and ion-exchange chromatography. The active receptors were isolated by alprenolol-sepharose CL-4B. The resulting level of purified human beta2-adrenergic receptor was approximately 1 mg per liter of culture. The homogeneity of the protein sample was confirmed by a dynamical light scattering analysis of the receptor's micellar solution.
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Cureus
November 2024
Department of Medicine and Surgery, University of Insubria, Varese, ITA.
Background: Obstructive sleep apnea syndrome (OSAS) is a chronic syndrome, affecting about 1%-5% of children. OSAS is characterized by increased resistance and collapse of the upper airways, with different degrees of severity requiring interventions ranging from lifestyle modifications to surgery. Sympathetic activity is increased in OSAS, and the reduction of disease symptoms, occurring after adenotonsillectomy, correlates with biomarkers indicating a reduced sympathetic response.
View Article and Find Full Text PDFbioRxiv
December 2024
Istanbul Medipol University, School of Engineering and Natural Sciences, Department of Biomedical Engineering, 34810, Istanbul, Turkey.
G protein-coupled receptor (GPCR) signaling is terminated by arrestin binding to a phosphorylated receptor. Binding propensity has been shown to be modulated by stabilizing the pre-activated state of arrestin through point mutations or C-tail truncation. Here, we hypothesize that pre-activated rotated states can be stabilized by small molecules, and this can promote binding to phosphorylation-deficient receptors, which underly a variety of human disorders.
View Article and Find Full Text PDFJ Phys Chem Lett
December 2024
Frankfurt Institute for Advanced Studies, Ruth-Moufang-Straße 1, 60438 Frankfurt am Main, Germany.
Horm Metab Res
December 2024
Apherese-Zentrum am Kortumpark, Bochum, Germany.
After the COVID-19 pandemic, many patients have reported chronic fatigue and severe post-exertional malaise, with symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The accumulation of agonistic receptor autoantibodies targeting beta-adrenergic (β1 and β2) and muscarinic (M3 and M4) neurotransmitter receptors may play a crucial role in the pathomechanism of both ME/CFS and post-COVID conditions. Therapeutic apheresis has been suggested as an effective treatment option for alleviating and mitigating symptoms in this desperate group of patients.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Department of Pathology, College of Korean Medicine, Dong-eui University, Busan, 47227, Republic of Korea. Electronic address:
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