7EA9

Crystal Structure of human lysyl-tRNA synthetase Y145H mutant

Summary for 7EA9

• Entry DOI: 10.2210/pdb7ea9/pdb
• Descriptor: Lysine--tRNA ligase, 5'-O-[(L-LYSYLAMINO)SULFONYL]ADENOSINE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: lysyl-trna synthetase, lysrs, disease related mutant, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 243411.45

Authors

Wu, S.,Hei, Z.,Zheng, L.,Zhou, J.,Liu, Z.,Wang, J.,Fang, P. (deposition date: 2021-03-06, release date: 2021-03-31, Last modification date: 2023-11-29)

Primary citation

Wu, S.,Hei, Z.,Zheng, L.,Zhou, J.,Liu, Z.,Wang, J.,Fang, P.
Structural analyses of a human lysyl-tRNA synthetase mutant associated with autosomal recessive nonsyndromic hearing impairment.
Biochem.Biophys.Res.Commun., 554:83-88, 2021

PubMed Abstract: Aminoacyl-tRNA synthetases (AARSs) catalyze the ligation of amino acids to their cognate tRNAs and therefore play an essential role in protein biosynthesis in all living cells. The KARS gene in human encodes both cytosolic and mitochondrial lysyl-tRNA synthetase (LysRS). A recent study identified a missense mutation in KARS gene (c.517T > C) that caused autosomal recessive nonsyndromic hearing loss. This mutation led to a tyrosine to histidine (YH) substitution in both cytosolic and mitochondrial LysRS proteins, and decreased their aminoacylation activity to different levels. Here, we report the crystal structure of LysRS YH mutant at a resolution of 2.5 Å. We found that the mutation did not interfere with the active center, nor did it cause any significant conformational changes in the protein. The loops involved in tetramer interface and tRNA anticodon binding site showed relatively bigger variations between the mutant and wild type proteins. Considering the differences between the cytosolic and mitochondrial tRNAs, we suggest that the mutation triggered subtle changes in the tRNA anticodon binding region, and the interferences were further amplified by the different D and T loops in mitochondrial tRNA, and led to a complete loss of the aminoacylation of mitochondrial tRNA.

PubMed: 33784510
DOI: 10.1016/j.bbrc.2021.03.093

Experimental method

X-RAY DIFFRACTION (2.5 Å)