Human ADORA2A Virus-Like Particles

The human adenosine A2A receptor (ADORA2A) is a G protein-coupled receptor (GPCR) that plays a key role in regulating physiological and pathological processes, particularly in the central nervous system and cardiovascular system. The structure of ADORA2A consists of seven transmembrane domains, an extracellular loop for ligand binding, and an intracellular region that interacts with G proteins or inhibitory proteins. As a key mediator of adenosine signaling, ADORA2A regulates neurotransmitter release, immune responses, and blood flow by binding extracellular adenosine (an endogenous purine nucleoside). ADORA2A is involved in neuroprotection, inflammation, and the sleep-wake cycle, making it a promising therapeutic target for diseases such as Parkinson''s disease, inflammatory diseases, and cancer immunotherapy.

The ADORA2A VLP is a non-infectious nanostructure designed to mimic the native conformation and function of the ADORA2A receptor within a lipid bilayer environment. Unlike traditional expression systems (such as soluble proteins or cell membranes), VLPs incorporate ADORA2A into a stable particle format, similar to a viral envelope, but without genetic material. This platform preserves the receptor''s tertiary structure, post-translational modifications, and ligand-binding properties, making it ideal for drug screening, antibody development, and structural biology. VLPs are typically produced by co-expressing ADORA2A with viral structural proteins (such as gag or envelope) in mammalian or insect cells, followed by purification by ultracentrifugation or chromatography. Advantages include high reproducibility, scalability, and compatibility with techniques such as cryo-electron microscopy, surface plasmon resonance (SPR), and flow cytometry. Furthermore, ADORA2A VLPs enable the study of receptor dimerization, allosteric regulation, and downstream signaling in a near-physiological setting, bridging the gap between in vitro and cell-based studies.