Related Experiment Video
Updated: Jul 4, 2025
09:57
Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach
Published on: December 17, 2016
6.7K
Visualizing chaperone-mediated multistep assembly of the human 20S proteasome
Frank Adolf1,2, Jiale Du1,2, Ellen A Goodall2,3
1Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Biorxiv : the Preprint Server for Biology
|February 8, 2024
Summary
Researchers visualized the human proteasome core particle assembly pathway using cryo-EM. This reveals how assembly factors and chaperones guide the step-by-step construction of this vital protein degradation machine.
Area of Science:
- Biochemistry and structural biology
- Molecular and cellular biology
Background:
- The proteasome core particle (CP) is a large, 28-subunit machine essential for protein degradation.
- Assembly of the CP requires dedicated factors and chaperones to ensure correct stepwise production.
Approach:
- Utilized cryo-electron microscopy (cryo-EM) to reconstruct seven human proteasome subcomplexes.
- Visualized key assembly intermediates, including chaperones and active site propeptides.
Key Points:
- Detailed molecular mechanisms governing the order of subunit addition during assembly.
- Demonstrated structural adaptations of subcomplexes and assembly factors to stabilize intermediates.
- Revealed how assembly intermediates rearrange to coordinate proteolytic activation and gated active site access.
Conclusions:
- Structural insights explain numerous prior biochemical and genetic findings.
- Established a novel method for analyzing multiprotein complex assembly intermediates.
- Illuminated specific roles of assembly factors and fundamental principles of proteasome biogenesis.
Related Concept Videos
02:41Protein Complex Assembly
10.6K
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.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
01:17The Proteasome Structure
753
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...
The proteasome is an...
753
03:00Molecular Chaperones and Protein Folding
18.0K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.0K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
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...
7.3K
01:32Assembly of Complex Microtubule Structures
1.8K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
1.8K
01:57Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K