Introduction of ADRB2

The β2-adrenergic receptor (β2AR, ADRB2) is a prototypic G-protein coupled receptor (GPCR). Like all GPCRs, the ADRB2 has seven transmembrane-spanning segments. This receptor is involved in the production of physiological responses to adrenaline and noradrenaline. Upon binding to specific agonists, several signaling pathways can be triggered. It is reported to couple predominantly with stimulatory Gα_s and to a lesser extent with inhibitory Gα_i to modulate the activity of adenylyl cyclase and mitogen-activated protein kinases (MAPKs). Besides, proteins can directly interact with ADRB2 to produce physiologically relevant outcomes in a G protein-independent manner. ADRB2 is widely expressed on cells of the pulmonary, cardiac, skeletal muscle, and immune systems.

Functions of ADRB2 Membrane Protein

Different polymorphic forms, point mutations, and downregulation of ADRB2 have been associated with various diseases. Firstly, ADRB2 participates in the physiologic responses of the lung, including bronchodilation and bronchoprotection, and thus it plays an important role in the asthma pathophysiology. A class of ADRB2 agonists, such as Albuterol and Salmeterol, is in current clinical use to treat asthma. Secondly, the activation of ADRB2 increases cardiac performance but can also induce deleterious effects such as cardiac arrhythmias or myocardial apoptosis, playing a critical role in the regulation of myocardial function. Thirdly, being located on immune cells, ADRB2 may play a role in immunomodulation. Additionally, due to their wide expression in the body, this receptor has been implicated in other diseases, such as Alzheimer’s disease, obesity, and type 2 diabetes. As a result, it is an important therapeutic target.

Fig.1 Beta-2 adrenergic receptor.

Applications of ADRB2 Membrane Protein in Literature

1. Meng K., et al. Design, synthesis and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor. Bioorganic & Medicinal Chemistry. 2018. 26(9): 2320-2330. PMID: 29588128

This study reported the design, synthesis and structure-activity relationships (SAR) of seven Cmpd-15 derivatives, which are small molecule negative allosteric modulator for the β2-adrenergic receptor.

2. Parmar V K., et al. Beta2-adrenergic receptor homodimers: Role of transmembrane domain 1 and helix 8 in dimerization and cell surface expression. Biochim Biophys Acta. 2016, 1859(9): 1445-1455. PMID: 27993566

This study investigated a potential role for transmembrane domain 1 (TMD1) and helix 8 (H8) in dimerization and plasma membrane expression of the functional β2-adrenergic receptor. Results showed that a TMD1/H8 interface was linked with ER export and expression of functional β2-AR.

3. Weichert D., et al. Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists. Bioorganic & Medicinal Chemistry. 2016, 24(12): 2641-2653. PMID: 27132867

This study described a structure-guided approach for the design, synthesis, and biological investigation of agonists that show agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D₂ receptor.

4. Komolov K E., et al. Structural and functional analysis of a β2-adrenergic receptor complex with GRK5. Cell. 2017, 169(3): 407. PMID: 28431242

This study used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry, electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor.

5. Noh H., et al. Beta2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications. Kidney International. 2017, 92(1): 101-113. PMID: 28396116

To identify drugs with the potential to target macrophage activation associated with diabetic vascular complications, the investigators used a cell-based assay to screen a compound library. They found that beta 2-adrenergic receptor agonists were the most potent inhibitors and they confirmed these effects using experimental diabetic animal models.

ADRB2 Preparation Options

Membrane proteins represent one of the most important targets for pharmaceutical companies but technical limitations have been a major hindrance to our understanding of the function and structure of such proteins. During the past decade, Creative Biolabs has devoted to the process development of membrane protein expression, solubilization, purification, and characterization. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ADRB2 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Our Magic™ Membrane Protein Production platform offers different preparation options for the reconstitution of ADRB2, including both the classical approaches and new technologies. Aided by our expert scientists, you can always find a suitable format for your particular project. contact us to start the conversation.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.