The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron microscopy, we visualize the key commitment steps orchestrating 48S remodeling in humans. The mRNA Kozak sequence facilitates mRNA scanning in the 48S open state and stabilizes the 48S closed state by organizing the contacts of eukaryotic initiation factors (eIFs) and ribosomal proteins and by reconfiguring mRNA structure. GTPase-triggered large-scale fluctuations of 48S-bound eIF2 facilitate eIF5B recruitment, transfer of initiator tRNA from eIF2 to eIF5B and the release of eIF5 and eIF2. The 48S-bound multisubunit eIF3 complex controls ribosomal subunit joining by coupling eIF exchange to gradual displacement of the eIF3c N-terminal domain from the intersubunit interface. These findings reveal the structural mechanism of ORF selection in human cells and explain how eIF3 could function in the context of the 80S ribosome.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41594-024-01378-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural basis for translational control by the human 48S initiation complex.
Nat Struct Mol Biol
September 2024
Project Group Molecular Machines in Motion, Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron microscopy, we visualize the key commitment steps orchestrating 48S remodeling in humans. The mRNA Kozak sequence facilitates mRNA scanning in the 48S open state and stabilizes the 48S closed state by organizing the contacts of eukaryotic initiation factors (eIFs) and ribosomal proteins and by reconfiguring mRNA structure.
View Article and Find Full Text PDFStructural basis of AUC codon discrimination during translation initiation in yeast.
Nucleic Acids Res
October 2024
Developmental Biology and Genetics, Indian Institute of Science, Bangalore-560012, India.
In eukaryotic translation initiation, the 48S preinitiation complex (PIC) scans the 5' untranslated region of mRNAs to search for the cognate start codon (AUG) with assistance from various eukaryotic initiation factors (eIFs). Cognate start codon recognition is precise, rejecting near-cognate codons with a single base difference. However, the structural basis of discrimination of near-cognate start codons was not known.
View Article and Find Full Text PDFTime difference between pad placement in single versus double external defibrillation: A live patient simulation model.
Resusc Plus
September 2024
Norwegian Air Ambulance Foundation, Department of Research and Development, Oslo, Norway.
Background: Out-of-hospital cardiac arrest (OHCA) cause significant patient morbidity and mortality. Double sequential external defibrillation (DSED) represents an alternative treatment for OHCA patients, but the use is currently reserved for patients in refractory ventricular fibrillation. However, OHCA patients may achieve return of spontaneous circulation earlier with the use of DSED as initial treatment.
View Article and Find Full Text PDFPotential Gradient-Driven Dual-Functional Electrochromic and Electrochemical Device Based on a Shared Electrode Design.
Adv Sci (Weinh)
July 2024
Jiangsu Key Laboratory of Advanced Metallic Materials, School of Materials Science and Engineering, Southeast University, Nanjing, 211189, China.
Article Synopsis
- The integration of electrochromic devices with energy storage systems in wearables is challenging due to the need for an open system design for replenishing oxidants.
- A new self-powered electrochromic device combines a Zn/MnO ionic battery with a Prussian blue (PB) electrochromic system, using shared electrodes for efficient coloring and bleaching processes.
- This innovative device shows impressive performance, including high optical contrast, quick switching speeds, and the ability to be fabricated into flexible designs suitable for next-gen wearable technology.
Unraveling the landscapes and regulation of scanning, leaky scanning, and 48S initiation complex conformations.
Cell Rep
May 2024
Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:
Article Synopsis
- - The study focuses on translation initiation and scanning processes, examining how the proteins eIF4G1 and eIF1 affect the formation of the translation initiation complex (48S).
- - The researchers used a technique called TCP-seq to analyze the organization of 48S and discovered that AUG context plays a significant role in determining the efficiency of translation initiation, especially in non-leaky genes.
- - Their findings reveal distinct classes of initiation complexes, with one class being crucial for early initiation and another indicating a potential late initiation process, highlighting the dynamic nature of protein interactions during translation.
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!