Related Experiment Video
Updated: Jun 7, 2026
08:59
Analysis of Protein Folding, Transport, and Degradation in Living Cells by Radioactive Pulse Chase
Published on: February 12, 2019
The folding pathway of alpha1-antitrypsin: avoiding the unavoidable
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. steve.bottomley@monash.edu.au
Proceedings of the American Thoracic Society
|October 30, 2010
Summary
Alpha-1 antitrypsin (AAT) folding is metastable, not the most stable form. Understanding AAT folding and misfolding is crucial for preventing related diseases.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- Alpha-1 antitrypsin (AAT) is a protein with a metastable native fold.
- This native fold is not the most stable conformation achievable by its amino acid sequence.
- More stable conformations arise from the insertion of the reactive center loop into the A β sheet.
Purpose of the Study:
- To review literature on alpha-1 antitrypsin folding over the past 20 years.
- To examine how AAT maintains its native metastable state.
- To explore the link between AAT folding, misfolding, and disease pathology.
Main Methods:
- Literature review of studies on alpha-1 antitrypsin folding.
- Analysis of structural conformations and their stability.
- Correlation of folding pathways with disease mechanisms.
Main Results:
- The native fold of AAT is inherently unstable.
- Alternative, more stable conformations exist.
- Susceptibility to mutations leading to dysfunction and disease is linked to accessible low-energy folds.
Conclusions:
- AAT's metastable nature makes it prone to misfolding.
- Understanding folding pathways is key to addressing AAT-related pathologies.
- Further research into AAT folding dynamics can inform therapeutic strategies.
Related Concept Videos
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...
01:22Protein Folding
Overview
01:22Protein Folding
Overview
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:00Molecular Chaperones and Protein Folding
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...