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Related Concept Videos

Initiation of Translation02:33

Initiation of Translation

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
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Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Termination of Translation01:44

Termination of Translation

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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Related Experiment Video

Updated: Jun 12, 2025

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

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Structural basis for translational control by the human 48S initiation complex.

Valentyn Petrychenko1, Sung-Hui Yi2,3, David Liedtke1

  • 1Project Group Molecular Machines in Motion, Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.

Nature Structural & Molecular Biology
|September 17, 2024
PubMed
Summary
This summary is machine-generated.

Human cells select mRNA start sites using a remodeled 48S complex. This process involves eukaryotic initiation factors (eIFs) and the Kozak sequence, ensuring accurate translation initiation for protein synthesis.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Eukaryotic mRNA translation initiation involves scanning by the 48S complex to find the start codon.
  • Remodeling of the 48S complex to an 80S ribosome is crucial for initiating elongation.

Purpose of the Study:

  • To visualize the structural mechanisms of 48S complex remodeling during translation initiation in humans.
  • To elucidate the roles of eukaryotic initiation factors (eIFs) and mRNA structure in Open Reading Frame (ORF) selection.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to capture structural snapshots of the human 48S complex.
  • Analysis of factor interactions and mRNA conformation within the remodeling complex.

Main Results:

  • The mRNA Kozak sequence stabilizes the 48S complex by organizing eIF and ribosomal protein contacts and altering mRNA structure.
  • GTPase activity of eIF2 drives conformational changes, facilitating recruitment of eIF5B and initiator tRNA, and release of eIF5 and eIF2.
  • The eIF3 complex regulates 80S ribosome subunit joining by coordinating eIF exchange with eIF3c domain displacement.

Conclusions:

  • Detailed structural insights into the mechanism of ORF selection in human translation.
  • Provides a structural basis for understanding the function of eIF3 in 80S ribosome assembly and translation initiation.