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Related Concept Videos

The Proteasome Structure01:17

The Proteasome Structure

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The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
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The Proteasome02:18

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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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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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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
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Protein Complex Assembly02:41

Protein Complex Assembly

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Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
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Related Experiment Video

Updated: Sep 12, 2025

Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach
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Structure of the TXNL1-bound proteasome.

Jingjing Gao1, Christopher Nardone2,3, Matthew C J Yip1

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA, USA.

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|August 6, 2025
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Summary

Thioredoxin-like protein 1 (TXNL1) binds the proteasome, enabling its degradation without ubiquitination during oxidative stress. This structural insight reveals a new mechanism for stress-induced protein clearance.

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Area of Science:

  • Cellular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Proteasomes are crucial for protein homeostasis, degrading proteins via regulated mechanisms.
  • The precise regulation of proteasomal degradation, especially in response to cellular stress, remains incompletely understood.
  • Thioredoxin-like protein 1 (TXNL1) is involved in cellular responses, but its proteasomal degradation pathway is unclear.

Purpose of the Study:

  • To elucidate the structural basis of TXNL1 interaction with the proteasome.
  • To understand the mechanism of TXNL1 degradation in response to oxidative stress.
  • To identify the proteasomal subunits involved in TXNL1 recognition.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of TXNL1 bound to the 19S proteasome regulatory particle.
  • Biochemical assays to assess TXNL1 degradation in cellular contexts.
  • Identification of protein-protein interactions between TXNL1 and proteasome subunits.

Main Results:

  • The cryo-EM structure reveals TXNL1 bound to the 19S regulatory particle of the proteasome.
  • Key interactions involve TXNL1 binding to proteasome subunits PSMD1 (Rpn2), PSMD4 (Rpn10), and PSMD14 (Rpn11).
  • Proteasome binding is essential for the ubiquitin-independent degradation of TXNL1 when cells are exposed to metal- or metalloid-induced oxidative stress.

Conclusions:

  • The study establishes a structural requirement for the stress-induced degradation of TXNL1.
  • This work uncovers a novel pathway for proteasomal degradation that is independent of ubiquitination.
  • The findings provide a structural framework for understanding how proteasomes target specific proteins during cellular stress.