CD73 is a multifunctional transmembrane glycoprotein composed of 523 amino acids encoded by the NT5E gene (located on 6q14-21), with a relative molecular weight of 70,000. It is anchored to the cell membrane through glycosylphosphatidylinositol (GPI). The CD73 protein consists of three domains: an N-terminal domain (27-317AA) containing two zinc ion binding sites and at least one N-glycosylation site located at asparagine 311; a C-terminal domain (337-549AA) with a substrate binding site, non-covalently bound to the membrane through a GPI anchor; and a short helix (318-336AA) connecting the N-terminal and C-terminal domains, controlling the enzyme's movement. CD73 exists in "open" and "closed" conformations, with the catalytic reaction requiring CD73 to transition from the open conformation to the closed conformation, exposing the active binding site to allow substrate binding.
CD73 is widely expressed on the surface of various human tissue cells, including lymphocytes, endothelial cells, and epithelial cells, regulating physiological functions such as epithelial ion exchange, fluid transport, platelet function, tissue hypoxia, and vascular leakage. It mainly participates in the following physiological processes: (1) influencing the salvage synthesis of purine nucleotides. Adenosine generated by CD73, regulated by CD39 and CD73, controls purine nucleotide generation, thereby regulating nucleotide signal transduction. (2) Catalyzing 5'-AMP, generating adenosine that binds to A1, A2A, A2B, and A3 adenosine receptors, producing different physiological effects through biological signal transduction. (3) Involvement in T cell activation. Adenosine produced by CD73 hydrolysis can activate immune cells, affecting immune cell proliferation, and can regulate CD4+ CD25+Treg cells, attenuating T cell immune responses.
