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Amazing structural revelations: How does the three-dimensional structure of the β2 adenosine receptor affect our health?
β2 adrenergic receptor (ADRB2) is a transmembrane β-adrenergic receptor that binds to epinephrine (also known as adrenaline). This receptor stimulates adenylate acylase through the trimeric Gs protein, thereby increasing the production of cAMP, ultimately triggering a series of physiological responses, such as smooth muscle relaxation and bronchial dilation. In 2012, Robert J. Lefkowitz and Brian Kopyka were awarded the Nobel Prize in Chemistry for their work on the β2-adrenergic receptor, which revealed important inner workings of G protein-coupled receptors.
The structure of the β2-adrenergic receptor is complex and variable, which makes it play a key role in human health.
Gene and structural characteristics
The gene encoding β2-adrenergic receptor in humans is ADRB2, which is intronless. Its different polymorphic forms and point mutations may be associated with nocturnal asthma, obesity and type 2 diabetes.
The three-dimensional structure of the β2-adrenergic receptor has been determined by using a fusion protein approach to increase the hydrophilic surface area of the protein, thereby facilitating crystal formation. In 2011, the crystal structure of the β2-adrenergic receptor-Gs protein complex was revealed. These studies revealed major conformational changes in the receptor, including a 14 Å outward movement of the intracellular end of transmembrane segment 6 and a 2.5 Å shift of the transmembrane segment 1. 5 significantly extended.
Operation Mechanism
β2 adenergic receptors are directly associated with L-type calcium channels CaV1.2. The receptor-channel complex is coupled to Gs protein, further activating adenylate acylase to generate cAMP and start protein kinase A, which in turn This leads to smooth muscle relaxation, which is the main reason for the vasodilatory effect of beta2 stimulation.
The composition of this signaling complex ensures rapid and specific intracellular signaling and is essential for the maintenance of health.
Health Effects
Muscular and skeletal system
Activation of the β2-adrenergic receptor leads to the proliferation and synthesis of skeletal muscle, which is why long-acting agonists such as clenbuterol are widely used by athletes. These uses are generally considered banned substances and are monitored by the World Anti-Doping Agency.
The use of these agonists in food-producing animals also shows potential in agriculture, although it is banned in many countries.
Circulatory system
In the heart, stimulation of the beta2 adenosine receptors helps increase cardiac output and heart rate. Although this effect is weaker than that of the beta-1 adenosine receptor, its function is still important for maintaining heart health. Additionally, it dilates the tiny arteries in the hepatic artery and skeletal muscles, helping to improve blood flow.
Eye effects
In the normal eye, beta 2 stimulation leads to increased aqueous humor production and elevated intraocular pressure, which requires caution in patients with glaucoma.
Digestive system
This receptor is also involved in glycogenolysis and gluconeogenesis in the liver, affecting the digestive process and the secretion of insulin and glucagon.
Conclusionβ2-adrenergic receptors play multiple roles in human health and disease. The diversity of their structures and the complexity of their operations provide scientists with new inspiration for research. However, do we fully understand the profound impact these receptors have on various systems in the body?
