AARS - Alanine-TRNA Ligase |Elisa - Clia - Antibody - Protein

Background:

AARS, also known as alanyl-tRNA synthetase, is an enzyme encoded by the AARS gene. It belongs to the family of aminoacyl-tRNA synthetases, which are essential enzymes involved in protein synthesis. AARS specifically catalyzes the ligation of alanine to its cognate transfer RNA (tRNA^Ala), a key step in the translation of genetic information into proteins. Dysregulation or mutations in the AARS gene can lead to aminoacyl-tRNA synthetase deficiencies, which may present clinically as neurological disorders and other multisystemic manifestations.

Structure:

AARS is a multidomain protein consisting of catalytic domains responsible for amino acid activation and tRNA binding. It contains an aminoacylation domain, which binds alanine and ATP to form the activated aminoacyl-adenylate intermediate, and a tRNA-binding domain, which interacts with tRNA^Ala to facilitate the transfer of alanine to the tRNA molecule.

Classification and Subtypes:

AARS is classified as an aminoacyl-tRNA synthetase and is specifically designated as alanine-tRNA synthetase due to its role in charging tRNA^Ala with alanine. While there are no known subtypes of AARS in humans, it is part of a larger family of aminoacyl-tRNA synthetases, each specific for a different amino acid.

Function and Biological Significance:

1. Aminoacylation of tRNA: AARS catalyzes the aminoacylation of tRNA^Ala by covalently attaching alanine to the 3' end of the tRNA molecule. This process, known as aminoacylation or charging, ensures that the correct amino acid is incorporated into the growing polypeptide chain during protein synthesis.
2. Accuracy of Protein Synthesis: AARS plays a critical role in maintaining the fidelity and accuracy of translation by ensuring that each tRNA molecule is correctly charged with its cognate amino acid. Errors in aminoacylation can lead to mistranslation and the incorporation of incorrect amino acids into proteins, potentially compromising cellular function.
3. Regulation of Translation: AARS activity is tightly regulated to coordinate protein synthesis with cellular demands. It may be regulated by factors such as post-translational modifications, protein-protein interactions, and feedback mechanisms involving amino acid availability and tRNA charging levels.

Relevant Clinical Issues:

1. Genetic Disorders: Mutations in the AARS gene have been associated with rare genetic disorders known as aminoacyl-tRNA synthetase deficiencies. These disorders are characterized by impaired protein synthesis due to defects in aminoacylation, leading to a wide range of clinical manifestations affecting multiple organ systems.
2. Neurological Disorders: Some aminoacyl-tRNA synthetase deficiencies, including those involving AARS mutations, manifest primarily as neurological disorders, with symptoms such as developmental delay, intellectual disability, epilepsy, and progressive neurodegeneration.
3. Therapeutic Implications: Understanding the molecular basis of AARS-related disorders is essential for developing targeted therapies aimed at correcting aminoacylation defects and restoring normal protein synthesis. Approaches such as gene therapy, enzyme replacement therapy, or small molecule modulators may hold promise for treating these conditions.