Conformational rearrangements upon start codon recognition in human 48S translation initiation complex.
Animals
Codon, Initiator
/ metabolism
Eukaryotic Initiation Factor-1
/ metabolism
Eukaryotic Initiation Factor-2
/ metabolism
Eukaryotic Initiation Factor-3
/ metabolism
Humans
Mammals
/ genetics
Peptide Chain Initiation, Translational
Ribosomes
/ metabolism
Saccharomyces cerevisiae
/ metabolism
Saccharomyces cerevisiae Proteins
/ metabolism
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 05 2022
20 05 2022
Historique:
accepted:
20
04
2022
revised:
08
04
2022
received:
02
03
2022
pubmed:
1
5
2022
medline:
25
5
2022
entrez:
30
4
2022
Statut:
ppublish
Résumé
Selection of the translation start codon is a key step during protein synthesis in human cells. We obtained cryo-EM structures of human 48S initiation complexes and characterized the intermediates of codon recognition by kinetic methods using eIF1A as a reporter. Both approaches capture two distinct ribosome populations formed on an mRNA with a cognate AUG codon in the presence of eIF1, eIF1A, eIF2-GTP-Met-tRNAiMet and eIF3. The 'open' 40S subunit conformation differs from the human 48S scanning complex and represents an intermediate preceding the codon recognition step. The 'closed' form is similar to reported structures of complexes from yeast and mammals formed upon codon recognition, except for the orientation of eIF1A, which is unique in our structure. Kinetic experiments show how various initiation factors mediate the population distribution of open and closed conformations until 60S subunit docking. Our results provide insights into the timing and structure of human translation initiation intermediates and suggest the differences in the mechanisms of start codon selection between mammals and yeast.
Identifiants
pubmed: 35489072
pii: 6576361
doi: 10.1093/nar/gkac283
pmc: PMC9122606
doi:
Substances chimiques
Codon, Initiator
0
Eukaryotic Initiation Factor-1
0
Eukaryotic Initiation Factor-2
0
Eukaryotic Initiation Factor-3
0
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5282-5298Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
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