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Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
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Post-translational Translocation of Proteins to the RER01:27

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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
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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.
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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...
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Cotranslational Protein Translocation01:20

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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.
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Related Experiment Video

Updated: Aug 13, 2025

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins
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Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins

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Studying Reversible Protein Post-translational Modification through Co-translational Modification.

Dan Wu1, Tao Liu1

  • 1State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Molecular and Cellular Pharmacology, Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Chembiochem : a European Journal of Chemical Biology
|January 24, 2023
PubMed
Summary

Genetic code expansion enables studying protein post-translational modifications in eukaryotes. This technology, combined with synthetic biology, creates genetically modified organisms for advanced research and future applications.

Keywords:
co-translational modificationsgenetic code expansiongenetically modified organismspost-translational modificationsunnatural amino acids

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Area of Science:

  • Chemical Biology
  • Molecular Biology
  • Synthetic Biology

Background:

  • Post-translational modifications (PTMs) are crucial for eukaryotic physiological processes.
  • Investigating PTMs at specific sites requires advanced chemical biology tools.

Purpose of the Study:

  • To review the applications, limitations, and future perspectives of genetic code expansion (GCE) for PTM research.
  • To discuss the development of genetically modified organisms (GMOs) utilizing GCE for PTM studies.

Main Methods:

  • Genetic code expansion (GCE) technology.
  • Synthetic biology approaches.
  • Creation of genetically modified organisms with synthetic auxotrophies.

Main Results:

  • GCE allows site-specific incorporation of non-canonical amino acids to study PTMs.
  • Combination of GCE with synthetic biology enables novel approaches for PTM investigation.
  • Recent progress highlights the versatility and potential of GCE.

Conclusions:

  • GCE is a powerful tool for understanding the biological roles of PTMs.
  • Future GMOs developed using GCE will advance PTM research.
  • This technology holds significant promise for manipulating eukaryotic physiological processes.