Weakening the IF2-fMet-tRNA Interaction Suppresses the Lethal Phenotype Caused by GTPase Inactivation.

Int J Mol Sci

Laboratory of Genetics, Department of Bioscience and Biotechnology, University of Camerino, 62032 Camerino, Italy.

Published: December 2021

Substitution of the conserved Histidine 448 present in one of the three consensus elements characterizing the guanosine nucleotide binding domain (IF2 G2) of translation initiation factor IF2 resulted in impaired ribosome-dependent GTPase activity which prevented IF2 dissociation from the ribosome, caused a severe protein synthesis inhibition, and yielded a dominant lethal phenotype. A reduced IF2 affinity for the ribosome was previously shown to suppress this lethality. Here, we demonstrate that also a reduced IF2 affinity for fMet-tRNA can suppress this dominant lethal phenotype and allows IF2 to support faithful translation in the complete absence of GTP hydrolysis. These results strengthen the premise that the conformational changes of ribosome, IF2, and fMet-tRNA occurring during the late stages of translation initiation are thermally driven and that the energy generated by IF2-dependent GTP hydrolysis is not required for successful translation initiation and that the dissociation of the interaction between IF2 C2 and the acceptor end of fMet-tRNA, which represents the last tie anchoring the factor to the ribosome before the formation of an elongation-competent 70S complex, is rate limiting for both the adjustment of fMet-tRNA in a productive P site and the IF2 release from the ribosome.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709274PMC
http://dx.doi.org/10.3390/ijms222413238DOI Listing

Publication Analysis

Top Keywords

lethal phenotype
12
translation initiation
12
if2
9
dominant lethal
8
reduced if2
8
if2 affinity
8
gtp hydrolysis
8
ribosome
5
weakening if2-fmet-trna
4
if2-fmet-trna interaction
4

Similar Publications

Want 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!