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Related Concept Videos

Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
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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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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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Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

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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...
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Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

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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
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
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Ribosomes01:27

Ribosomes

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Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
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Updated: Jun 23, 2025

Single Molecule Fluorescence Energy Transfer Study of Ribosome Protein Synthesis
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Structural analysis of the dynamic ribosome-translocon complex.

Aaron J O Lewis1, Frank Zhong2, Robert J Keenan3

  • 1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

Elife
|June 19, 2024
PubMed
Summary

The protein translocon machinery dynamically adjusts its structure and composition, revealing novel configurations for protein biogenesis. Unexpectedly, RAMP4 is found within the Sec61 complex, altering its pore properties.

Keywords:
cell biologyendoplasmic reticulummammalmembrane protein insertionmembrane transportmolecular biophysicssecretionstructural biologytranslocon

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Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Cell Biology

Background:

  • The protein translocon facilitates the biogenesis of secretory and membrane proteins at the endoplasmic reticulum.
  • It comprises the Sec61 translocation channel and various accessory factors.

Purpose of the Study:

  • To investigate novel configurations of the ribosome-translocon complex using cryo-electron microscopy (cryo-EM) and structure prediction.
  • To elucidate the mechanisms of protein insertion and translocon function.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
  • Structure prediction algorithms to model complex interactions.
  • Analysis of ribosome-translocon complex configurations.

Main Results:

  • Observed transmembrane domains (TMDs) in looped configurations passing through the Sec61 lateral gate.
  • Identified nascent chain binding and constraint of ribosomal protein uL22.
  • Showed dynamic positioning of the translocon-associated protein (TRAP) complex.
  • Discovered RAMP4 intercalated into Sec61's lateral gate in many complexes, widening the pore.

Conclusions:

  • The translocon is a plastic machinery with dynamically adjusting conformations and composition.
  • RAMP4's presence influences Sec61 pore properties, suggesting a role in protein translocation.
  • These findings provide mechanistic hypotheses for translocon function in diverse protein biogenesis pathways.