Related Experiment Video
Updated: Sep 30, 2025
06:58
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
2.6K
Ribosome-nascent Chain Interaction Regulates N-terminal Protein Modification
Chien-I Yang1, Jiwoo Kim1, Shu-Ou Shan1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, United States.
Journal of Molecular Biology
|March 12, 2022
Summary
The ribosome regulates N-terminal methionine excision (NME) by controlling nascent polypeptide access to enzymes. Hydrophobic sequences near the N-terminus inhibit NME, impacting protein modification during translation.
Area of Science:
- Molecular Biology
- Protein Biochemistry
- Cellular Biology
Background:
- Proteins undergo folding, localization, and modifications during translation.
- The ribosome plays an active role in protein biogenesis.
- N-terminal methionine excision (NME) is a crucial protein modification in bacteria.
Purpose of the Study:
- To investigate the ribosome's role in substrate selection during cotranslational N-terminal methionine excision (NME).
- To determine how nascent polypeptide features influence NME efficiency.
- To understand the impact of N-terminal hydrophobic sequences on NME in vivo.
Main Methods:
- Biochemical analyses of cotranslational NME.
- Investigating the effect of hydrophobic signal sequences on NME efficiency.
- In vivo measurements of NME in bacteria.
Main Results:
- Cotranslational NME is sensitive to hydrophobic signal sequences or transmembrane domains near the N-terminus.
- Nascent chain confinement on the ribosome surface inhibits NME efficiency.
- Signal recognition particle exacerbates NME inhibition.
- In vivo studies confirm NME inhibition by N-terminal hydrophobic sequences.
Conclusions:
- The ribosome actively participates in protein biogenesis by regulating cotranslational modifications like NME.
- Nascent protein features, such as N-terminal hydrophobicity, dictate modification efficiency.
- Ribosome-nascent chain interactions influence protein processing and the proteome composition.
Related Concept Videos
01:34Directing Proteins to the Rough Endoplasmic Reticulum
10.0K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
10.0K
02:53Ribosomal RNA Synthesis
13.6K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
13.6K
01:26Bacterial Protein Maturation
123
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
123
01:27Post-translational Translocation of Proteins to the RER
6.0K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
6.0K
01:23Regulation of Expression at Multiple Steps
1.1K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.1K
01:20Cotranslational Protein Translocation
7.8K
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...
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...
7.8K