Related Experiment Video
Updated: Aug 11, 2026
09:54
Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
Published on: August 20, 2018
Alpha 1-antitrypsin polymerisation can occur by both loop A and C sheet mechanisms
S P Bottomley1, P C Hopkins, J C Whisstock
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3168, Australia. steve.bottomley@med.monash.edu.au
Biochemical and Biophysical Research Communications
|October 29, 1998
Summary
Alpha1-antitrypsin polymerization causes disease. This study shows alpha1-antitrypsin uses both loop A-sheet and C-sheet mechanisms, depending on buffer conditions, clarifying disease pathways.
Area of Science:
- Biochemistry and Molecular Biology
- Protein Misfolding Diseases
- Cellular Pathology
Background:
- Alpha1-antitrypsin polymerization in hepatocytes leads to endoplasmic reticulum stress and plasma deficiency.
- This polymerization is implicated in various disease states.
- Two proposed polymerization mechanisms exist: loop A-sheet and C-sheet.
Purpose of the Study:
- To investigate the polymerization mechanisms of alpha1-antitrypsin.
- To determine if alpha1-antitrypsin can undergo both proposed polymerization pathways.
- To elucidate the influence of in vitro conditions on polymerization mechanisms.
Main Methods:
- Utilized fluorescence studies with alpha1-antitrypsin modified with pyrene maleimide.
- Conducted detailed molecular modeling studies.
- Analyzed polymerization under varying in vitro buffer conditions.
Main Results:
- Demonstrated that alpha1-antitrypsin can undergo polymerization via the loop A-sheet mechanism.
- Showed that alpha1-antitrypsin can also polymerize through the loop C-sheet mechanism.
- Confirmed that the specific polymerization pathway is dependent on the in vitro buffer conditions.
Conclusions:
- Alpha1-antitrypsin is capable of adopting both loop A-sheet and loop C-sheet polymerization mechanisms.
- In vitro buffer conditions dictate which polymerization pathway is favored.
- This finding provides a more comprehensive understanding of alpha1-antitrypsin polymerization relevant to disease pathogenesis.
Related Concept Videos
01:13Protein Organization
Overview
01:22Protein Folding
Overview
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
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...
01:24Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
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...