Related Experiment Video

Updated: Aug 16, 2026

Amyloid and the Cross-Beta Architecture
09:06

Amyloid and the Cross-Beta Architecture

Published on: February 13, 2026

Seeding-dependent propagation and maturation of amyloid fibril conformation

Kei-Ichi Yamaguchi1, Satoshi Takahashi, Tomoji Kawai

  • 1Institute for Protein Research, Osaka University, and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.

Journal of Molecular Biology
|August 30, 2005
PubMed

Insights

Beta2-microglobulin peptide fragments form two distinct amyloid fibrils. These fibrils exhibit conformational maturation through self-seeding, offering insights into amyloidosis development.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Biophysics

Background:

  • Amyloid fibrils can adopt multiple conformations, influencing disease.
  • Beta2-microglobulin is implicated in dialysis-related amyloidosis.
  • Understanding fibril polymorphism and propagation is crucial for disease mechanisms.

Purpose of the Study:

  • To elucidate the structural basis of amyloid fibril polymorphism and conformational memory.
  • To investigate the formation and propagation of different amyloid structures from a single protein fragment.
  • To explore the phenomenon of conformational maturation in amyloid fibrils.

Main Methods:

  • Utilized the amyloidogenic K3 fragment of beta2-microglobulin.
  • Induced fibril formation in a solution of 2,2,2-trifluoroethanol and HCl.
  • Characterized fibril structures using circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and atomic force microscopy.
  • Investigated fibril propagation and maturation through seeding experiments.

Main Results:

  • Two distinct amyloid-like fibrils, f218 and f210, were formed from the K3 peptide.
  • Fibrils differed in beta-sheet content, with f210 being thinner and longer.
  • Both fibril types demonstrated template-dependent propagation via seeding.
  • Repeated self-seeding led to the gradual transformation of f218 into f210 fibrils (conformational maturation).

Conclusions:

  • Amyloid fibril formation can yield distinct structural variants from a single precursor.
  • Conformational memory and maturation are key features of amyloid propagation.
  • The competitive propagation of different fibril forms explains observed maturation.
  • Fibril maturation may contribute to the pathogenesis of amyloidosis.

More Related Videos

Rapid Generation of Amyloid from Native Proteins In vitro05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo09:44

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo

Published on: June 2, 2019

Related Concept Videos

Amyloid Fibrils03:03

Amyloid 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 Fibrils03:03

Amyloid 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...
Protein Folding01:25

Protein 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 Folding01:22

Protein Folding

Overview
Protein Folding Quality Check in the RER01:29

Protein 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...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...