The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS). ScIleRS utilizes a eukaryotic/archaeal-specific arginine as the H-bond donor to recognize the common carbonyl group (H-bond acceptor) of various N34s of tRNA, which induces mutual structural adaptations between ScIleRS and tRNA to achieve a preferable editing state. C34 of unmodified tRNA(CAU) (behaves like tRNA) lacks a relevant H-bond acceptor, which disrupts key H-bonding interactions and structural adaptations and suspends the ScIleRS·tRNA(CAU) complex in an initial non-reactive state. This wobble nucleotide recognition-based structural adaptation provides mechanistic insights into selective tRNA aminoacylation by AARSs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41467-024-55183-0 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685878 | PMC |
Publication Analysis
Top Keywords
Similar Publications
The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition.
Nat Commun
December 2024
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS).
View Article and Find Full Text PDFAn approach to target multiple proteins involved in anti-microbial resistance using natural compounds produced by wild mushrooms.
Biochem Biophys Rep
December 2024
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.
Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS).
View Article and Find Full Text PDFCochlear Implantation for Isoleucyl-tRNA Synthetase Mutation-Associated Mitochondrial Disease: A Case Report.
Cureus
August 2024
Department of Human Health Science and Therapeutics, The Jikei University School of Nursing, Chofu, JPN.
Article Synopsis
- Biallelic missense mutations in the IARS gene can lead to a complex set of health issues including growth delays, intellectual disabilities, muscle weakness, diabetes, and hearing loss.
- Despite IARS being a cytosolic enzyme, these mutations can cause mitochondrial dysfunction, linking them to the diverse clinical symptoms observed.
- A case study of a Japanese woman with severe hearing loss due to IARS mutations showed that cochlear implantation effectively restored her hearing, with no reported complications from general anesthesia during the procedure.
Inhibition of Epidermal Isoleucyl-tRNA Synthetase Ameliorates Psoriasis-Like Skin Lesions through Jak2/Signal Transducer and Activator of Transcription 3/CXCL16 Signaling Pathway.
J Invest Dermatol
September 2024
Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:
IARS2 mutations lead to Leigh syndrome with a combined oxidative phosphorylation deficiency.
Orphanet J Rare Dis
August 2024
Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Background: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!