EC Number   |
General Information |
Reference |
|---|
    6.1.1.7 | evolution |
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family |
745185 |
| 6.1.1.7 | evolution |
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Tetrapisispora phaffii possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Phylogenetic relationships of yeast AlaRSs, overview |
745765 |
| 6.1.1.7 | evolution |
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Vanderwaltozyma polyspora possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Clever selection of transcription and translation initiation sites enables the two isoforms to be localized and thus functional in their respective cellular compartments. But the two isoforms can also be stably expressed and function in the reciprocal compartments by insertion or removal of a mitochondrial targeting signal. Synteny and phylogeny analyses reveal that the AlaRS homologues of Vanderwaltozyma polyspora arose from a dual-functional common ancestor through whole-genome duplication (WGD). Moreover, the mitochondrial form has higher synonymous (1.6fold) and nonsynonymous (2.8fold) substitution rates than does its cytoplasmic counterpart, presumably due to a lesser constraint imposed on components of the mitochondrial translational apparatus. Asymmetric evolution confers the divergence between the AlaRS paralogues of Vanderwaltozyma polyspora. Phylogenetic relationships of yeast AlaRSs, overview |
-, 745765 |
| 6.1.1.7 | evolution |
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. The AlaRS homologues of Saccharomyces cerevisiae arose from a dual-functional common ancestor through whole-genome duplication (WGD), but retains only one copy of the AlaRS gene. Phylogenetic relationships of yeast AlaRSs, overview |
745765 |
| 6.1.1.7 | evolution |
the enzyme belongs to the class IIa aminoacyl-tRNA synthetase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Tetrapisispora phaffii possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Phylogenetic relationships of yeast AlaRSs, overview |
745765 |
| 6.1.1.7 | evolution |
the enzyme is constituted by three domains with an evolutionarily conserved modular arrangement: the N-terminal aminoacylation domain, the editing domain and the C-terminal domain (C-Ala). Alanyl-tRNA synthetases (AlaRSs) belong to class-II aminoacyl-tRNA synthetases |
-, 744473 |
| 6.1.1.7 | evolution |
the sequence of appended C-terminal domain (C-Ala) of enzyme AlaRS diverged widely in the evolutionary progression to humans. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS. Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, show that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS. This reshaping removed the role of C-Ala in prokaryotes for docking tRNA and instead repurposed it to form a dimer interface presenting a DNA-binding groove. This groove cannot form with the bacterial ortholog. Direct DNA binding by human C-Ala, but not by bacterial C-Ala. Instead of acquiring a special appended domain, a new AlaRS architecture has benn created by diversifying a preexisting domain |
746308 |
| 6.1.1.7 | malfunction |
enzyme mutations are associated with infantile mitochondrial cardiomyopathy |
726653 |
| 6.1.1.7 | malfunction |
importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is recognized as a disease gene for mitochondrial disease. Mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) is observed both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. The cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. All mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. The cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. Molecular basis of the distinct tissue-specific phenotypic outcomes of enzyme mutantions, structure analysis and homology modeling, overview |
744969 |
| 6.1.1.7 | more |
enzyme structure modeling, analysis of the contact surface between linker safety belt, and beta-barrel of the editing domain in modeled human mitochondrial AlaRS, overview |
744969 |
