9w01 | pdb_00009w01

Cryo-EM structure of LARS1:IARS1 complex

spinqualitylabelsall models 9w01, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9w01 is a 2 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 3.16Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SYLC_HUMAN Acute infantile liver failure-multisystemic involvement syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function SYLC_HUMAN Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs. Publication Abstract from PubMed Aminoacyl-tRNA synthetases (ARSs) assemble into the multi-tRNA synthetase complex (MSC) to mediate noncanonical functions in cell signaling and stress responses. Among them, human cytosolic leucyl-tRNA synthetase 1 (LARS1) plays a central role in sensing leucine and activating mTORC1, thereby linking nutrient availability to metabolic regulation. Despite recent progress, fundamental questions remain unresolved about the regulatory mechanisms governing LARS1's non-canonical functions, particularly its structural organization within the MSC. Here, we employ an integrated approach combining structural, biochemical, and cellular analyses to investigate the noncanonical roles of LARS1. The cryo-EM structure of the LARS1:isoleucyl-tRNA synthetase 1 (IARS1) complex reveals that LARS1 binds to IARS1, its anchoring partner in the MSC, via its UNE-L domain. Amino acid stimulation induces LARS1 phosphorylation at Ser1070, Ser1077, and Ser1082, which are located at the interface with IARS1. These modifications disrupt the interaction, promote LARS1 dissociation from the MSC, and enable mTORC1 activation. This study highlights phosphorylation as a conserved and critical molecular switch that orchestrates the non-canonical functions of MSC by dynamically modulating the assembly and activity of its components in response to external stimuli. Cryo-EM structure of the LARS1:IARS1 complex reveals a nutrient-responsive switch controlling mTORC1 signaling.,Kim Y, Kim JC, Kim DW, Kim J, Choi J, Park SY, Lee J, Yoon I, Kim S, Kang JY, Park HS Nat Commun. 2026 Jun 11. doi: 10.1038/s41467-026-74085-x. PMID:42276995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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