Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins.

摘要: Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From metabolic point of view, deaminase (ADA) essential protein the regulation total intracellular extracellular tissue. In addition to its cytosolic localization, ADA also expressed ecto-enzyme on surface different cells. Dipeptidyl peptidase IV (CD26) some ARs act binding proteins for humans. Since CD26 interact with at opposite sites, we have investigated if can function cell-to-cell communication molecule by bridging anchoring molecules A2AR present surfaces interacting By combining site-directed mutagenesis amino acids involved modification bioluminescence resonance energy transfer (BRET) technique allows detection interactions between two cell populations low steric hindrance (NanoBRET), show direct evidence specific formation trimeric complexes CD26-ADA-A2AR involving dynamic mass redistribution assays ligand experiments, demonstrate A2AR-NanoLuc fusion functional. The existence this ternary complex good agreement hypothesis could bridge T-cells (expressing CD26) dendritic cells A2AR). This new ecto-ADA that, being single chain protein, it has been considered example moonlighting because performs more than one functional role (as catalyst, costimulator, allosteric modulator connector) without partitioning these functions subunits.