Related Experiment Video
Updated: Jul 2, 2026
05:48
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Amylin proprotein processing generates progressively more amyloidogenic peptides that initially sample the helical
Isaac T Yonemoto1, Gerard J A Kroon, H Jane Dyson
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Biochemistry
|August 20, 2008
Summary
Human amylin, a peptide linked to type 2 diabetes, forms amyloid deposits. This study found amylin aggregates faster than its intermediates, suggesting diabetes-related stress, not intermediates, initiates amyloid formation in beta cells.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Human amylin (islet amyloid polypeptide) is co-secreted with insulin by pancreatic beta cells.
- Amylin forms intracellular and extracellular amyloid deposits in type II diabetes, linked to impaired beta cell function.
- Amylin processing intermediates are implicated in initiating intracellular amyloidogenesis.
Purpose of the Study:
- To investigate the in vitro amyloid formation propensity of human amylin and its processing intermediates.
- To compare the kinetics and characteristics of amylin and intermediate aggregation under physiological conditions.
Main Methods:
- Size exclusion chromatography was used to obtain monomeric amylin and intermediates.
- Nuclear Magnetic Resonance (NMR) spectroscopy characterized peptide conformations.
- Aggregation assays were performed under conditions mimicking the immature secretory granule.
Main Results:
- Human amylin adopts helical conformations in solution.
- Amylin formed amyloid aggregates more rapidly than its processing intermediates under simulated secretory granule conditions.
- Peptide amyloidogenicity negatively correlated with net charge and C-terminal charge.
Conclusions:
- Amylin aggregation is faster than its intermediates under specific conditions.
- The findings suggest that amylin processing intermediates may not initiate amyloidogenesis in stressed beta cells.
- Defects in protein homeostasis control in diabetes are more likely drivers of amylin amyloid deposition.
Related Concept Videos
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...
01:13Protein Organization
Overview
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...
01:22Protein Folding
Overview