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Crystal structure of human wild type GlyRS bound with tRNAGly
Structural highlights
DiseaseGARS_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2D;Distal hereditary motor neuropathy type 5. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionGARS_HUMAN Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017).[1] [2] [3] [4] Publication Abstract from PubMedAminoacyl-tRNA synthetases are essential components of the protein translational machinery in all living species, among which the human glycyl-tRNA synthetase (hGlyRS) is of great research interest because of its unique species-specific aminoacylation properties and noncanonical roles in the Charcot-Marie-Tooth neurological disease. However, the molecular mechanisms of how the enzyme carries out its classical and alternative functions are not well understood. Here, we report a complex structure of the wild-type hGlyRS bound with tRNAGly at 2.95A. In the complex, the flexible Whep-TRS domain is visible in one of the subunits of the enzyme dimer, and the tRNA molecule is also completely resolved. At the active site, a glycyl-AMP molecule is synthesized and is waiting for the transfer of the glycyl moiety to occur. This cocrystal structure provides us with new details about the recognition mechanism in the intermediate stage during glycylation, which was not well elucidated in the previous crystal structures where the inhibitor AMPPNP was used for crystallization. More importantly, the structural and biochemical work conducted in the current and previous studies allows us to build a model of the full-length hGlyRS in complex with tRNAGly, which greatly helps us to understand the roles that insertions and the Whep-TRS domain play in the tRNA-binding process. Finally, through structure comparison with other class II aminoacyl-tRNA synthetases bound with their tRNA substrates, we found some commonalities of the aminoacylation mechanism between these enzymes. Crystal Structure of the Wild-Type Human GlyRS Bound with tRNAGly in a Productive Conformation.,Qin X, Deng X, Chen L, Xie W J Mol Biol. 2016 May 31. pii: S0022-2836(16)30187-5. doi:, 10.1016/j.jmb.2016.05.018. PMID:27261259[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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