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Valyl-tRNA Synthetase

Valyl-tRNA synthetase (ValRS, also known as valine tRNA ligase) is the enzyme responsible for charging tRNA(val) with valine. In humans, ValRS exists in a cytosolic and a mitochondrial form. The cytosolic form is a monomeric 140kDa protein encoded by VARS1 while the mitochondrial form is a slightly smaller monomeric 118kDa protein encoded by VARS2. ValRS is a member of the class-Ia subfamily of aminoacyl-tRNA synthetases, defined by a characteristic α helix bundle at the C-terminus used for tRNA recognition. Aminoacyl-tRNA synthetases are generally highly conserved, and ValRS exhibits high structural similarity to IleRS and LeuRS. Human disease related to mutations in ValRS are very rare but life-threatening. Biallelic mutations in ValRS are associated with neurological defects and global developmental delay, including epileptic encephalopathy, microcephaly and microphthalmia^[1]. These phenotypes are thought to be due to a global lack of charged tRNA molecules which induces an amino acid starvation response and inhibits cell proliferation^[2].

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Structural Overview The major structural elements of ValRS, like other class-Ia aminoacyl-tRNA synthetases, are a helical insertion into the N-terminal half of a Rossmann fold domain and an α-helix bundle domain near the C-terminus[3]. Additionally, ValRS has a large editing domain important in the discrimination between valine and structurally similar amino acids. A positively charged (SC-fold) domain contacts C11 and C25 of the D-loop of tRNA(val), creating a space between the anticodon recognition and editing domains where the tRNA is "pinched" and held onto. This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

1. ↑ doi: https://dx.doi.org/doi.org/10.1038/s41467-018-07067-3
2. ↑ doi: https://dx.doi.org/doi.org/10.3389/fcell.2019.00067
3. ↑ doi: https://dx.doi.org/10.1261/rna.2760703