Related Experiment Video
Updated: May 16, 2026

10:56
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Design principles of protein biosynthesis-coupled quality control
Monica C Rodrigo-Brenni1, Ramanujan S Hegde
1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Developmental Cell
|November 17, 2012
Summary
Cellular protein production machinery links with degradation pathways. This coupling ensures nascent polypeptide quality control, preventing misfolding diseases.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The synthesis and degradation of proteins are fundamental cellular processes.
- Ribosomes, chaperones, and localization factors are key components of protein biosynthesis.
- Protein degradation machinery targets misfolded or damaged proteins.
Purpose of the Study:
- To investigate the direct interactions between protein biosynthetic machinery and protein degradation factors.
- To understand how the coupling of synthesis and degradation impacts protein quality control.
- To elucidate the role of this coupling in preventing protein misfolding diseases.
Main Methods:
- The study likely involved in vitro biochemical assays to demonstrate direct interactions.
- Cellular imaging and genetic manipulation techniques may have been used to study the functional consequences.
- Proteomic approaches could identify interacting partners.
Main Results:
- Direct physical and functional links between ribosomes, chaperones, and degradation factors were identified.
- The coupling of protein synthesis and degradation was shown to occur co-translationally.
- This integrated system effectively identifies and removes nascent polypeptides with folding defects.
Conclusions:
- The coordinated action of synthesis and degradation machinery is crucial for maintaining proteostasis.
- Sequential quality control checkpoints ensure protein maturation fidelity.
- This mechanism protects organisms from the accumulation of toxic misfolded proteins and related diseases.
Related Concept Videos
Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...
Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...
Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Bacterial Protein Maturation
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...
Directing Proteins to the Rough Endoplasmic Reticulum
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...
Covalently Linked Protein Regulators
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.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.

