Fig. 2

In silico analysis of HARS2 variants. a Multispecies sequence alignment of the HARS2 protein showing the evolutionary conservation of two mutated amino acids (p.Asp117Asn and p.Leu303Pro). Red shading indicates amino acids shared among all eight species. b Newly identified and previously reported HARS2 variants are marked along the schematic representation of HARS2. The N-terminal catalytic domain (amino acid; aa 1–405) and the C-terminal anticodon binding domain (aa 406–506). The catalytic domain contains the highly conserved dimer interface shown in dark blue (aa 65–177) and the histidine recognition and binding sites shown in pink (HisA: aa 327–332 and HisB: aa 361–365) c Crystal-structure-based in silico modeling of a dimeric HARS2 protein. This 3D model of the HARS2 protein is based on the structure of dimeric human HisRS (PDB ID 4phc). Two monomers of the homodimer are shown in green and blue, respectively. The Asp117 residue is located in the s1 loop at the dimer interface, as indicated by the red stick. The Leu303residue is located in an α-helix displayed in orange. d Close-up view of residue 117 and other residues that interacted. e Close-up view of residue 303 and other residues that interacted