2013
DOI: 10.1261/rna.042069.113
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Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates initiation accuracy

Abstract: In the current model of translation initiation by the scanning mechanism, eIF1 promotes an open conformation of the 40S subunit competent for rapidly loading the eIF2·GTP·Met-tRNA i ternary complex (TC) in a metastable conformation (P OUT ) capable of sampling triplets entering the P site while blocking accommodation of Met-tRNA i in the P IN state and preventing completion of GTP hydrolysis (P i release) by the TC. All of these functions should be reversed by eIF1 dissociation from the preinitiation complex (… Show more

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Cited by 38 publications
(43 citation statements)
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“…Met were chased with excess unlabeled TC, incubated for increasing time periods, and then resolved via native gel electrophoresis to separate 40S-bound and unbound fractions of TC. In agreement with previous findings (11,29,30), little to no TC dissociation occurred from WT PICs formed with the AUG-containing mRNA [mRNA(AUG)] over the time course Fig. 2A with the indicated RPS3 alleles were cultured in SD+His+Trp+Ura medium to an A 600 of ∼1.0 and WCEs were subjected to Western analysis using antibodies against eIF1 or Hcr1 (as loading control).…”
Section: Rps3supporting
confidence: 90%
“…Met were chased with excess unlabeled TC, incubated for increasing time periods, and then resolved via native gel electrophoresis to separate 40S-bound and unbound fractions of TC. In agreement with previous findings (11,29,30), little to no TC dissociation occurred from WT PICs formed with the AUG-containing mRNA [mRNA(AUG)] over the time course Fig. 2A with the indicated RPS3 alleles were cultured in SD+His+Trp+Ura medium to an A 600 of ∼1.0 and WCEs were subjected to Western analysis using antibodies against eIF1 or Hcr1 (as loading control).…”
Section: Rps3supporting
confidence: 90%
“…One explanation might be that the predicted reduction in k on for 43SÁmRNA(UUG) complexes conferred by slower TC loading to the open/P OUT state is offset by an increase of nearly equal magnitude in the rate of P OUT -to-P IN isomerization at UUG but not AUG codons. To explain why G70A would selectively accelerate the P OUT -to-P IN transition at UUG, it could be proposed that G70A perturbs interaction of Met-tRNA i with eIF2 in a way that alters the orientation of TC in the P site to favor base-pairing with UUG, which entails a U:U mismatch at the first position of the codon:anticodon duplex but not for the perfect codon:anticodon duplex at AUG. We came to a similar conclusion recently regarding the SUI5 mutation in eIF5 that stabilizes P IN at UUG while destabilizing it at AUG (Martin-Marcos et al 2014).…”
Section: Evidence That Substituting G70 Destabilizes the Open/p Out Csupporting
confidence: 83%
“…It is also clear that eIF5 plays an important role in initiation codon selection, most likely through changes in direct and indirect interactions with eIF1, eIF1A, and eIF2 on the surface of the 40 S subunit (11,15,48). Although we have not determined whether there is a contribution of eIF5 on the overall stability of the 43 S PIC, we do not observe any influence of eIF5 on the stability of eIF1, eIF1A, or eIF3j individually with the 40 S subunit (Table 1).…”
Section: Discussionmentioning
confidence: 99%