Related Experiment Video
Updated: Jul 13, 2026
09:26
Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones
Published on: March 26, 2017
Posttranslational quality control: folding, refolding, and degrading proteins.
S Wickner1, M R Maurizi, S Gottesman
1Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Science (New York, N.Y.)
|December 3, 1999
Summary
Protein folding quality control relies on molecular chaperones and proteases. The balance between these systems determines protein fate, preventing aggregation and amyloid diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- Newly synthesized polypeptides emerging from ribosomes require proper folding into stable three-dimensional structures to maintain cellular function.
- Cellular protein quality control mechanisms, including molecular chaperones and proteases, are essential for managing protein structure and function.
- These quality control systems recognize exposed hydrophobic regions on unfolded or misfolded polypeptides.
Purpose of the Study:
- To elucidate the critical roles of molecular chaperones and proteases in maintaining protein homeostasis.
- To investigate the kinetics of polypeptide partitioning between chaperones and proteases and its impact on protein fate.
- To understand the link between the failure of these quality control mechanisms and the accumulation of aggregated proteins in amyloid diseases.
Main Methods:
- This study focuses on the functional interplay between molecular chaperones and proteases in polypeptide quality control.
- It examines the recognition of hydrophobic regions by these machinery.
- The kinetics of partitioning between chaperones and proteases are analyzed to determine protein folding outcomes.
Main Results:
- Molecular chaperones facilitate proper protein folding and inhibit aggregation.
- Energy-dependent proteases selectively eliminate irreversibly damaged proteins.
- The rate at which polypeptides are directed to chaperones versus proteases dictates whether they are successfully folded or targeted for degradation.
Conclusions:
- The balance between chaperone-mediated folding and protease-mediated degradation is crucial for cellular protein quality control.
- Failure in these pathways leads to the accumulation of misfolded proteins, contributing to the pathogenesis of amyloid diseases.
- Understanding these kinetics is vital for developing therapeutic strategies against protein misfolding disorders.
More Related Videos
11:17Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
10:31Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability
Published on: February 3, 2022
Related Concept Videos
01:22Protein Folding
Overview
02:11Proteins: 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...
01:29Protein 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...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
02:11Proteins: 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...
01:26Bacterial 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...