The initiation factor 3 (IF3) residues interacting with initiator tRNA elbow modulate the fidelity of translation initiation and growth fitness in Escherichia coli.

Autor:	Singh J; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India., Mishra RK; Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India., Ayyub SA; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India., Hussain T; Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India., Varshney U; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.; Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2022 Nov 11; Vol. 50 (20), pp. 11712-11726.
DOI:	10.1093/nar/gkac1053
Abstrakt:	Initiation factor 3 (IF3) regulates the fidelity of bacterial translation initiation by debarring the use of non-canonical start codons or non-initiator tRNAs and prevents premature docking of the 50S ribosomal subunit to the 30S pre-initiation complex (PIC). The C-terminal domain (CTD) of IF3 can carry out most of the known functions of IF3 and sustain Escherichia coli growth. However, the roles of the N-terminal domain (NTD) have remained unclear. We hypothesized that the interaction between NTD and initiator tRNAfMet (i-tRNA) is essential to coordinate the movement of the two domains during the initiation pathway to ensure fidelity of the process. Here, using atomistic molecular dynamics (MD) simulation, we show that R25A/Q33A/R66A mutations do not impact NTD structure but disrupt its interaction with i-tRNA. These NTD residues modulate the fidelity of translation initiation and are crucial for bacterial growth. Our observations also implicate the role of these interactions in the subunit dissociation activity of CTD of IF3. Overall, the study shows that the interactions between NTD of IF3 and i-tRNA are crucial for coupling the movements of NTD and CTD of IF3 during the initiation pathway and in imparting growth fitness to E. coli. (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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