HARS Human

Histidyl-tRNA synthetase (HRS), also known as Jo-1, is an enzyme that plays a crucial role in protein synthesis. It belongs to the class of aminoacyl-tRNA synthetases, which are responsible for attaching amino acids to their corresponding tRNA molecules, a key step in translating genetic information into proteins .

HRS is a homodimeric enzyme, meaning it consists of two identical subunits. It catalyzes the ATP-dependent ligation of histidine to the 3’-end of its cognate tRNA, forming an aminoacyl-adenylate intermediate (His-AMP) . This process is essential for the accurate incorporation of histidine into polypeptide chains during protein synthesis.

HRS is notably associated with the anti-synthetase syndrome, a subset of idiopathic inflammatory myopathies (IIM). This syndrome is characterized by myositis, inflammatory arthritis, interstitial lung disease (ILD), and other systemic manifestations . Anti-Jo-1 antibodies, which target HRS, are commonly found in patients with this syndrome and are used as a diagnostic marker .

Recombinant HRS is produced using genetic engineering techniques, typically expressed in Escherichia coli (E. coli). This recombinant form is used in various research applications, including studies on autoimmune diseases and protein synthesis . The recombinant enzyme has a molecular mass of approximately 55 kDa and is supplied in a solution containing urea, NaCl, and Trizma-HCl buffer .

Research on HRS has provided insights into its role in both innate and adaptive immune responses. It has been shown to activate Toll-like receptors and their downstream signaling pathways, contributing to the immunopathogenesis of the anti-synthetase syndrome . Understanding these mechanisms is crucial for developing targeted therapies for autoimmune diseases associated with HRS.