Related Experiment Video
Updated: May 11, 2026
08:53
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
Published on: March 21, 2025
Hydrogen bonding involving side chain exchangeable groups stabilizes amyloid quarternary structure
Vipin Agarwal1, Rasmus Linser, Muralidhar Dasari
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin-Buch, Germany.
Physical Chemistry Chemical Physics : PCCP
|May 31, 2013
Summary
Researchers discovered that amino acid side chains, like histidines, can reveal how amyloid fibrils assemble in Alzheimer's disease. This finding helps understand the quaternary structure of these disease-related protein aggregates.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Amyloid β-peptide (Aβ) forms amyloid fibrils, the main component of plaques in Alzheimer's disease brains.
- While secondary and tertiary structures of fibrils are studied, the mechanisms driving protofilament association into bundles remain unknown.
Purpose of the Study:
- To investigate the mechanisms of protofilament association into amyloid fibril bundles.
- To identify factors that can provide restraints for determining the quaternary assembly of amyloid fibrils.
Main Methods:
- Utilizing amino acid side chain exchangeable groups, such as histidines, as restraints.
- Employing a deuteration method where exchangeable deuterons are substituted with protons before fibril formation.
Main Results:
- Amino acid side chain exchangeable groups can provide restraints for determining quaternary fibril assembly.
- Exchangeable protons are observable when side chain hydrogen bonds form and protect protons from exchange.
Conclusions:
- Amino acid side chain properties offer insights into the quaternary assembly of amyloid fibrils.
- The study provides a novel method to investigate fibril bundling mechanisms in Alzheimer's disease.
Related Concept Videos
01:22Protein Folding
Overview
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
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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...
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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
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Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
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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.