8ffy

Cryo-electron microscopy structure of human mt-SerRS in complex with mt-tRNA(UGA-TL)

spinqualitylabelsall models 8ffy, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ffy is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: N, SSA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SYSM_HUMAN Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome. The disease is caused by variants affecting the gene represented in this entry. Function SYSM_HUMAN Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).[UniProtKB:Q9N0F3] Publication Abstract from PubMed Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNA(Ser) isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNA(Ser(UGA)), and perform a structural and functional comparison with the mSerRS-mtRNA(Ser(GCU)) complex. We find that despite their common function, mtRNA(Ser(UGA)) and mtRNA(Ser(GCU)) show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNA(Ser). Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes. Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition.,Kuhle B, Hirschi M, Doerfel LK, Lander GC, Schimmel P Nat Commun. 2023 Aug 9;14(1):4794. doi: 10.1038/s41467-023-40354-2. PMID:37558671 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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